Ashley Jenkins, MD

Venous thromboembolism (VTE) is a life-threatening event occurring with increasing frequency in hospitalized children and an incidence of more than 58 events per 10,000 hospitalizations.¹ In pediatric patients, VTEs occur less often than in adults, have bimodal peaks in neonates and adolescents, and are typically provoked, with central venous access as the most common risk factor.^1,

Treatment of pediatric VTE includes unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and vitamin K antagonists (ie, warfarin). These agents have limitations, including parenteral administration, frequent lab monitoring, and drug/dietary interactions complicating use. Only recently have there been pediatric studies to assess these agents’ pharmacokinetics, pharmacodynamics, safety, and efficacy.²

Direct oral anticoagulants (DOACs) commonly used to treat VTE in adults have two mechanisms of action: direct thrombin (activated factor II) inhibition (ie, dabigatran) and activated factor X (Xa) inhibition (ie, rivaroxaban, apixaban, edoxaban, betrixaban). DOACs offer practical advantages over and efficacy similar to that of warfarin and heparin products, including oral administration, predictable pharmacology, no required lab monitoring, and fewer drug/dietary interactions. DOACs are already approved for VTE treatment in patients 18 years and older.³

This clinical practice update synthesizes 6 years (2014-2020) of literature regarding DOACs for treatment of VTE, focusing on their current role in patients 18 years and older and their emerging role in pediatric patients.

DOACs are approved by the US Food and Drug Administration (FDA) for multiple anticoagulation indications in adults, including treatment and prevention of acute VTE and prevention of stroke in nonvalvular atrial fibrillation (Table). DOACs are well tolerated by most adults; however, use in certain populations, including patients with liver disease with coagulopathy, advanced renal disease (creatinine clearance <30 mL/min), and class III obesity (body mass index [BMI] >40 kg/m²), requires caution.^4,5 For adult patients with VTE without contraindications, DOACs are considered equivalent to warfarin; current CHEST guidelines even suggest preference of DOACs over warfarin.⁵ While it is prudent to exercise caution when extrapolating adult data to children, these data have informed ongoing pediatric DOAC clinical trials.

The efficacy and safety of each of the DOACs (aside from betrixaban, which is indicated only for prophylaxis) have compared with warfarin for treatment of VTE in adults.⁶ A meta-analysis of six clinical trials determined DOACs are noninferior to warfarin for VTE treatment.³ Only two of six trials included patients with provoked VTEs. The meta-analysis found no difference in rates of recurrent symptomatic VTE (primary outcome; relative risk [RR], 0.91; 95% CI, 0.79-1.06) or all-cause mortality (secondary outcome; RR, 0.98; 95% CI, 0.84-1.14). Additionally, DOACs were shown as possibly safer than warfarin due to fewer major bleeding events, particularly fatal bleeding (RR, 0.36; 95% CI, 0.15-0.84) and intracranial bleeding (RR, 0.34; 95% CI, 0.17-0.69). For clinically relevant nonmajor bleeding (eg, gastrointestinal bleeding requiring <2 U packed red blood cells), results were similar (RR, 0.73; 95% CI, 0.58-0.93).

DOACs appear to have effectiveness comparable with that of warfarin. A retrospective matched cohort study of 59,525 patients with acute VTE compared outcomes of patients on DOACs (95% on rivaroxaban) with those of patients on warfarin.⁶ There were no differences in all-cause mortality or major bleeding. Another retrospective cohort study of 62,431 patients with acute VTE compared rivaroxaban and apixaban with warfarin, as well as rivaroxaban and apixaban with each other.⁷ There were no differences in 3- and 6-month mortality between warfarin and DOAC users or between rivaroxaban and apixaban users.

Initial approval of DOACs brought concerns about reversibility in the setting of bleeding or urgent procedural need. Clinical practice guidelines, primarily based on observational studies and laboratory parameters in vitro or in healthy volunteers, recommend activated prothrombin complex concentrates as a first-line intervention.⁸ However, specific agents have now been FDA-approved for DOAC reversal.

Idarucizumab is an FDA-approved (2015) monoclonal antibody with high affinity for dabigatran. Approval was based on a multicenter prospective cohort study of 503 patients taking dabigatran who presented with major bleeding (301 patients) or requiring an urgent surgery (202 patients).⁹ Idarucizumab resulted in a median time to bleeding cessation of 2.5 hours for those 134 patients in whom time to bleeding cessation could be assessed. Patients with intracranial bleeding were excluded from the timed portion because follow up imaging was not mandated. For those requiring surgery, 93% had normal periprocedural hemostasis.

Andexanet alfa is an FDA-approved (2018) drug for reversal of apixaban and rivaroxaban that acts as a catalytically inactive decoy Xa molecule, binding Xa inhibitors with high affinity. A multicenter prospective cohort study of 352 patients on Xa inhibitors with major bleeding found administration of andexanet alfa resulted in excellent or good hemostasis in 82% of patients (204/249 patients) at 12 hours.¹⁰ There was no difference between rivaroxaban and apixaban patients. Both idarucizumab and andexanet alfa remain expensive and not universally available, but availability and use will likely increase with time.

In pediatric patients, most VTEs are provoked, with the most common risk factor being presence of a central line. Frequency of this risk factor varies based on age (>60% of cases in older children and nearly 90% in neonates).¹ The most recent American Society of Hematology guidelines recommend treating pediatric symptomatic VTE with anticoagulation and treating asymptomatic VTE instead of observation.² These recommendations rely on evidence in adult patients due to the current paucity of evidence in pediatrics.

“Pediatric investigation plans” are the cornerstone for ongoing clinical trials of DOACs in pediatrics. While studies evaluating safety and efficacy of standard anticoagulants (UFH, LMWH, and warfarin) in pediatrics exist, clinical trials at the time of drug development did not include pediatric patients. This means none of the currently used anticoagulants were initially developed or approved for children.¹ Under the Pediatric Research Equity Act of 2007, the FDA requires pharmaceutical companies to submit a New Drug Application to perform pediatric studies of drugs deemed likely for use in pediatric patients. Pediatric investigation plans allow for establishing safety, efficacy, dosing, and administration routes in pediatric populations. All four DOACs currently approved for treatment of VTE in adults have ongoing efficacy and safety clinical trials for children.

The first and only published clinical trial of DOAC efficacy and safety in pediatrics compared rivaroxaban to standard treatment of acute VTE (Appendix Table).¹¹ The industry-sponsored, open-label EINSTEIN-Jr trial randomized patients aged 0 to 17 years 2:1 to weight-based rivaroxaban or standard treatment after receiving initial parenteral therapy for 5 to 9 days. While most patients were treated for at least 3 months, patients younger than 2 years with line-related thrombosis were treated for only 1 month. The study population mostly consisted of patients with initial, symptomatic, provoked VTE, with types ranging from cerebral venous sinus thrombosis to catheter-associated thrombosis. VTE risk factors, which varied by age, included presence of a central line, major infection, surgery, or trauma. While most VTEs in pediatric patients are expected to be central-line related, in the EINSTEIN-Jr trial only 25.2% of VTEs were central line–associated. The study evaluated symptomatic recurrent VTE (primary efficacy outcome) and clinically relevant bleeding (safety outcome). No significant difference was found between treatment groups in efficacy or safety outcomes, and there were no treatment-related deaths. While the trial was not powered to assess noninferiority due to low incidence of VTE in pediatrics, the absolute number of symptomatic recurrent VTEs was lower in the rivaroxaban group compared with the standard-care group (1% vs 3%). The investigators concluded that rivaroxaban is similarly efficacious and safe in children as compared with adults. FDA approval of rivaroxaban in pediatrics is expected given the trial’s favorable results. Clinicians may wish to consider whether the studied population is comparable with their own patients because the trial had a lower percentage of line-associated VTE than previously reported in the pediatric population.

Multiple clinical trials evaluating the efficacy and safety of other DOACs in pediatric patients are currently underway (Appendix Table).^12-14 Apixaban and edoxaban have active multicenter, randomized, open-label clinical trials recruiting patients up to age 17 who have imaging-confirmed acute VTE. A similar trial for dabigatran has recently completed recruitment. Outcome measures include recurrent VTE, VTE-related mortality, and major or clinically relevant non-major bleeding. Like EINSTEIN-Jr, patients in the dabigatran and edoxaban trials were treated with parenteral therapy for at least 5 days prior to randomization.^12,14 In the apixaban trial, participants can be randomized without initial parenteral treatment.¹³ Betrixaban, the newest DOAC approved in adults, does not currently have any open pediatric trials.

Lack of approved reversal agents may initially limit DOAC use in children. An open-label study examining idarucizumab safety has completed enrollment, but it has not yet published results.¹⁵ To date, there are no pediatric clinical trials examining andexanet alpha. Future work will need to establish efficacy and safety of reversal agents in pediatrics.

DOACs have not been adequately studied in populations of patients with comorbidities, such as liver disease, renal disease, altered enteral absorption, and BMI higher than 40. Physiologic differences in children with cancer and in neonates merit further evaluation of DOAC safety and efficacy. While ongoing trials established weight-based dosing regimens for children, longitudinal studies will need to ensure adequate anticoagulation, especially in the populations listed here.

The safety outcomes in most DOAC studies include clinically relevant bleeding and VTE-related mortality. These outcomes are much less common in pediatric patients than they are in adults, and future studies may need to expand safety outcomes to those more frequently seen in children. Primary and secondary endpoint variability in pediatric DOAC clinical trials presents challenges interpreting and comparing study results.

VTE is an increasingly common complication in hospitalized children contributing to significant morbidity.¹ For decades, the only treatment options have been UFH, LMWH, or warfarin. DOACs offer many advantages compared with standard anticoagulation options. The only clinical trial evaluating efficacy and safety of DOACs published to date demonstrates that pediatric patients taking rivaroxaban have outcomes similar to those of patients receiving standard care. It is expected that DOACs will gain FDA approval for treatment of VTE in pediatric patients in the near future; therefore, hospitalists should understand indications for use of these medications.

Venous thromboembolism (VTE) is a life-threatening event occurring with increasing frequency in hospitalized children and an incidence of more than 58 events per 10,000 hospitalizations.¹ In pediatric patients, VTEs occur less often than in adults, have bimodal peaks in neonates and adolescents, and are typically provoked, with central venous access as the most common risk factor.^1,

Treatment of pediatric VTE includes unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and vitamin K antagonists (ie, warfarin). These agents have limitations, including parenteral administration, frequent lab monitoring, and drug/dietary interactions complicating use. Only recently have there been pediatric studies to assess these agents’ pharmacokinetics, pharmacodynamics, safety, and efficacy.²

Direct oral anticoagulants (DOACs) commonly used to treat VTE in adults have two mechanisms of action: direct thrombin (activated factor II) inhibition (ie, dabigatran) and activated factor X (Xa) inhibition (ie, rivaroxaban, apixaban, edoxaban, betrixaban). DOACs offer practical advantages over and efficacy similar to that of warfarin and heparin products, including oral administration, predictable pharmacology, no required lab monitoring, and fewer drug/dietary interactions. DOACs are already approved for VTE treatment in patients 18 years and older.³

This clinical practice update synthesizes 6 years (2014-2020) of literature regarding DOACs for treatment of VTE, focusing on their current role in patients 18 years and older and their emerging role in pediatric patients.

DOACs are approved by the US Food and Drug Administration (FDA) for multiple anticoagulation indications in adults, including treatment and prevention of acute VTE and prevention of stroke in nonvalvular atrial fibrillation (Table). DOACs are well tolerated by most adults; however, use in certain populations, including patients with liver disease with coagulopathy, advanced renal disease (creatinine clearance <30 mL/min), and class III obesity (body mass index [BMI] >40 kg/m²), requires caution.^4,5 For adult patients with VTE without contraindications, DOACs are considered equivalent to warfarin; current CHEST guidelines even suggest preference of DOACs over warfarin.⁵ While it is prudent to exercise caution when extrapolating adult data to children, these data have informed ongoing pediatric DOAC clinical trials.

The efficacy and safety of each of the DOACs (aside from betrixaban, which is indicated only for prophylaxis) have compared with warfarin for treatment of VTE in adults.⁶ A meta-analysis of six clinical trials determined DOACs are noninferior to warfarin for VTE treatment.³ Only two of six trials included patients with provoked VTEs. The meta-analysis found no difference in rates of recurrent symptomatic VTE (primary outcome; relative risk [RR], 0.91; 95% CI, 0.79-1.06) or all-cause mortality (secondary outcome; RR, 0.98; 95% CI, 0.84-1.14). Additionally, DOACs were shown as possibly safer than warfarin due to fewer major bleeding events, particularly fatal bleeding (RR, 0.36; 95% CI, 0.15-0.84) and intracranial bleeding (RR, 0.34; 95% CI, 0.17-0.69). For clinically relevant nonmajor bleeding (eg, gastrointestinal bleeding requiring <2 U packed red blood cells), results were similar (RR, 0.73; 95% CI, 0.58-0.93).

DOACs appear to have effectiveness comparable with that of warfarin. A retrospective matched cohort study of 59,525 patients with acute VTE compared outcomes of patients on DOACs (95% on rivaroxaban) with those of patients on warfarin.⁶ There were no differences in all-cause mortality or major bleeding. Another retrospective cohort study of 62,431 patients with acute VTE compared rivaroxaban and apixaban with warfarin, as well as rivaroxaban and apixaban with each other.⁷ There were no differences in 3- and 6-month mortality between warfarin and DOAC users or between rivaroxaban and apixaban users.

Initial approval of DOACs brought concerns about reversibility in the setting of bleeding or urgent procedural need. Clinical practice guidelines, primarily based on observational studies and laboratory parameters in vitro or in healthy volunteers, recommend activated prothrombin complex concentrates as a first-line intervention.⁸ However, specific agents have now been FDA-approved for DOAC reversal.

Idarucizumab is an FDA-approved (2015) monoclonal antibody with high affinity for dabigatran. Approval was based on a multicenter prospective cohort study of 503 patients taking dabigatran who presented with major bleeding (301 patients) or requiring an urgent surgery (202 patients).⁹ Idarucizumab resulted in a median time to bleeding cessation of 2.5 hours for those 134 patients in whom time to bleeding cessation could be assessed. Patients with intracranial bleeding were excluded from the timed portion because follow up imaging was not mandated. For those requiring surgery, 93% had normal periprocedural hemostasis.

Andexanet alfa is an FDA-approved (2018) drug for reversal of apixaban and rivaroxaban that acts as a catalytically inactive decoy Xa molecule, binding Xa inhibitors with high affinity. A multicenter prospective cohort study of 352 patients on Xa inhibitors with major bleeding found administration of andexanet alfa resulted in excellent or good hemostasis in 82% of patients (204/249 patients) at 12 hours.¹⁰ There was no difference between rivaroxaban and apixaban patients. Both idarucizumab and andexanet alfa remain expensive and not universally available, but availability and use will likely increase with time.

In pediatric patients, most VTEs are provoked, with the most common risk factor being presence of a central line. Frequency of this risk factor varies based on age (>60% of cases in older children and nearly 90% in neonates).¹ The most recent American Society of Hematology guidelines recommend treating pediatric symptomatic VTE with anticoagulation and treating asymptomatic VTE instead of observation.² These recommendations rely on evidence in adult patients due to the current paucity of evidence in pediatrics.

“Pediatric investigation plans” are the cornerstone for ongoing clinical trials of DOACs in pediatrics. While studies evaluating safety and efficacy of standard anticoagulants (UFH, LMWH, and warfarin) in pediatrics exist, clinical trials at the time of drug development did not include pediatric patients. This means none of the currently used anticoagulants were initially developed or approved for children.¹ Under the Pediatric Research Equity Act of 2007, the FDA requires pharmaceutical companies to submit a New Drug Application to perform pediatric studies of drugs deemed likely for use in pediatric patients. Pediatric investigation plans allow for establishing safety, efficacy, dosing, and administration routes in pediatric populations. All four DOACs currently approved for treatment of VTE in adults have ongoing efficacy and safety clinical trials for children.

The first and only published clinical trial of DOAC efficacy and safety in pediatrics compared rivaroxaban to standard treatment of acute VTE (Appendix Table).¹¹ The industry-sponsored, open-label EINSTEIN-Jr trial randomized patients aged 0 to 17 years 2:1 to weight-based rivaroxaban or standard treatment after receiving initial parenteral therapy for 5 to 9 days. While most patients were treated for at least 3 months, patients younger than 2 years with line-related thrombosis were treated for only 1 month. The study population mostly consisted of patients with initial, symptomatic, provoked VTE, with types ranging from cerebral venous sinus thrombosis to catheter-associated thrombosis. VTE risk factors, which varied by age, included presence of a central line, major infection, surgery, or trauma. While most VTEs in pediatric patients are expected to be central-line related, in the EINSTEIN-Jr trial only 25.2% of VTEs were central line–associated. The study evaluated symptomatic recurrent VTE (primary efficacy outcome) and clinically relevant bleeding (safety outcome). No significant difference was found between treatment groups in efficacy or safety outcomes, and there were no treatment-related deaths. While the trial was not powered to assess noninferiority due to low incidence of VTE in pediatrics, the absolute number of symptomatic recurrent VTEs was lower in the rivaroxaban group compared with the standard-care group (1% vs 3%). The investigators concluded that rivaroxaban is similarly efficacious and safe in children as compared with adults. FDA approval of rivaroxaban in pediatrics is expected given the trial’s favorable results. Clinicians may wish to consider whether the studied population is comparable with their own patients because the trial had a lower percentage of line-associated VTE than previously reported in the pediatric population.

Multiple clinical trials evaluating the efficacy and safety of other DOACs in pediatric patients are currently underway (Appendix Table).^12-14 Apixaban and edoxaban have active multicenter, randomized, open-label clinical trials recruiting patients up to age 17 who have imaging-confirmed acute VTE. A similar trial for dabigatran has recently completed recruitment. Outcome measures include recurrent VTE, VTE-related mortality, and major or clinically relevant non-major bleeding. Like EINSTEIN-Jr, patients in the dabigatran and edoxaban trials were treated with parenteral therapy for at least 5 days prior to randomization.^12,14 In the apixaban trial, participants can be randomized without initial parenteral treatment.¹³ Betrixaban, the newest DOAC approved in adults, does not currently have any open pediatric trials.

Lack of approved reversal agents may initially limit DOAC use in children. An open-label study examining idarucizumab safety has completed enrollment, but it has not yet published results.¹⁵ To date, there are no pediatric clinical trials examining andexanet alpha. Future work will need to establish efficacy and safety of reversal agents in pediatrics.

DOACs have not been adequately studied in populations of patients with comorbidities, such as liver disease, renal disease, altered enteral absorption, and BMI higher than 40. Physiologic differences in children with cancer and in neonates merit further evaluation of DOAC safety and efficacy. While ongoing trials established weight-based dosing regimens for children, longitudinal studies will need to ensure adequate anticoagulation, especially in the populations listed here.

The safety outcomes in most DOAC studies include clinically relevant bleeding and VTE-related mortality. These outcomes are much less common in pediatric patients than they are in adults, and future studies may need to expand safety outcomes to those more frequently seen in children. Primary and secondary endpoint variability in pediatric DOAC clinical trials presents challenges interpreting and comparing study results.

VTE is an increasingly common complication in hospitalized children contributing to significant morbidity.¹ For decades, the only treatment options have been UFH, LMWH, or warfarin. DOACs offer many advantages compared with standard anticoagulation options. The only clinical trial evaluating efficacy and safety of DOACs published to date demonstrates that pediatric patients taking rivaroxaban have outcomes similar to those of patients receiving standard care. It is expected that DOACs will gain FDA approval for treatment of VTE in pediatric patients in the near future; therefore, hospitalists should understand indications for use of these medications.

Venous thromboembolism (VTE) is a life-threatening event occurring with increasing frequency in hospitalized children and an incidence of more than 58 events per 10,000 hospitalizations.¹ In pediatric patients, VTEs occur less often than in adults, have bimodal peaks in neonates and adolescents, and are typically provoked, with central venous access as the most common risk factor.^1,

Treatment of pediatric VTE includes unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and vitamin K antagonists (ie, warfarin). These agents have limitations, including parenteral administration, frequent lab monitoring, and drug/dietary interactions complicating use. Only recently have there been pediatric studies to assess these agents’ pharmacokinetics, pharmacodynamics, safety, and efficacy.²

Direct oral anticoagulants (DOACs) commonly used to treat VTE in adults have two mechanisms of action: direct thrombin (activated factor II) inhibition (ie, dabigatran) and activated factor X (Xa) inhibition (ie, rivaroxaban, apixaban, edoxaban, betrixaban). DOACs offer practical advantages over and efficacy similar to that of warfarin and heparin products, including oral administration, predictable pharmacology, no required lab monitoring, and fewer drug/dietary interactions. DOACs are already approved for VTE treatment in patients 18 years and older.³

This clinical practice update synthesizes 6 years (2014-2020) of literature regarding DOACs for treatment of VTE, focusing on their current role in patients 18 years and older and their emerging role in pediatric patients.

DOACs are approved by the US Food and Drug Administration (FDA) for multiple anticoagulation indications in adults, including treatment and prevention of acute VTE and prevention of stroke in nonvalvular atrial fibrillation (Table). DOACs are well tolerated by most adults; however, use in certain populations, including patients with liver disease with coagulopathy, advanced renal disease (creatinine clearance <30 mL/min), and class III obesity (body mass index [BMI] >40 kg/m²), requires caution.^4,5 For adult patients with VTE without contraindications, DOACs are considered equivalent to warfarin; current CHEST guidelines even suggest preference of DOACs over warfarin.⁵ While it is prudent to exercise caution when extrapolating adult data to children, these data have informed ongoing pediatric DOAC clinical trials.

The efficacy and safety of each of the DOACs (aside from betrixaban, which is indicated only for prophylaxis) have compared with warfarin for treatment of VTE in adults.⁶ A meta-analysis of six clinical trials determined DOACs are noninferior to warfarin for VTE treatment.³ Only two of six trials included patients with provoked VTEs. The meta-analysis found no difference in rates of recurrent symptomatic VTE (primary outcome; relative risk [RR], 0.91; 95% CI, 0.79-1.06) or all-cause mortality (secondary outcome; RR, 0.98; 95% CI, 0.84-1.14). Additionally, DOACs were shown as possibly safer than warfarin due to fewer major bleeding events, particularly fatal bleeding (RR, 0.36; 95% CI, 0.15-0.84) and intracranial bleeding (RR, 0.34; 95% CI, 0.17-0.69). For clinically relevant nonmajor bleeding (eg, gastrointestinal bleeding requiring <2 U packed red blood cells), results were similar (RR, 0.73; 95% CI, 0.58-0.93).

DOACs appear to have effectiveness comparable with that of warfarin. A retrospective matched cohort study of 59,525 patients with acute VTE compared outcomes of patients on DOACs (95% on rivaroxaban) with those of patients on warfarin.⁶ There were no differences in all-cause mortality or major bleeding. Another retrospective cohort study of 62,431 patients with acute VTE compared rivaroxaban and apixaban with warfarin, as well as rivaroxaban and apixaban with each other.⁷ There were no differences in 3- and 6-month mortality between warfarin and DOAC users or between rivaroxaban and apixaban users.

Initial approval of DOACs brought concerns about reversibility in the setting of bleeding or urgent procedural need. Clinical practice guidelines, primarily based on observational studies and laboratory parameters in vitro or in healthy volunteers, recommend activated prothrombin complex concentrates as a first-line intervention.⁸ However, specific agents have now been FDA-approved for DOAC reversal.

Idarucizumab is an FDA-approved (2015) monoclonal antibody with high affinity for dabigatran. Approval was based on a multicenter prospective cohort study of 503 patients taking dabigatran who presented with major bleeding (301 patients) or requiring an urgent surgery (202 patients).⁹ Idarucizumab resulted in a median time to bleeding cessation of 2.5 hours for those 134 patients in whom time to bleeding cessation could be assessed. Patients with intracranial bleeding were excluded from the timed portion because follow up imaging was not mandated. For those requiring surgery, 93% had normal periprocedural hemostasis.

Andexanet alfa is an FDA-approved (2018) drug for reversal of apixaban and rivaroxaban that acts as a catalytically inactive decoy Xa molecule, binding Xa inhibitors with high affinity. A multicenter prospective cohort study of 352 patients on Xa inhibitors with major bleeding found administration of andexanet alfa resulted in excellent or good hemostasis in 82% of patients (204/249 patients) at 12 hours.¹⁰ There was no difference between rivaroxaban and apixaban patients. Both idarucizumab and andexanet alfa remain expensive and not universally available, but availability and use will likely increase with time.

In pediatric patients, most VTEs are provoked, with the most common risk factor being presence of a central line. Frequency of this risk factor varies based on age (>60% of cases in older children and nearly 90% in neonates).¹ The most recent American Society of Hematology guidelines recommend treating pediatric symptomatic VTE with anticoagulation and treating asymptomatic VTE instead of observation.² These recommendations rely on evidence in adult patients due to the current paucity of evidence in pediatrics.

“Pediatric investigation plans” are the cornerstone for ongoing clinical trials of DOACs in pediatrics. While studies evaluating safety and efficacy of standard anticoagulants (UFH, LMWH, and warfarin) in pediatrics exist, clinical trials at the time of drug development did not include pediatric patients. This means none of the currently used anticoagulants were initially developed or approved for children.¹ Under the Pediatric Research Equity Act of 2007, the FDA requires pharmaceutical companies to submit a New Drug Application to perform pediatric studies of drugs deemed likely for use in pediatric patients. Pediatric investigation plans allow for establishing safety, efficacy, dosing, and administration routes in pediatric populations. All four DOACs currently approved for treatment of VTE in adults have ongoing efficacy and safety clinical trials for children.

The first and only published clinical trial of DOAC efficacy and safety in pediatrics compared rivaroxaban to standard treatment of acute VTE (Appendix Table).¹¹ The industry-sponsored, open-label EINSTEIN-Jr trial randomized patients aged 0 to 17 years 2:1 to weight-based rivaroxaban or standard treatment after receiving initial parenteral therapy for 5 to 9 days. While most patients were treated for at least 3 months, patients younger than 2 years with line-related thrombosis were treated for only 1 month. The study population mostly consisted of patients with initial, symptomatic, provoked VTE, with types ranging from cerebral venous sinus thrombosis to catheter-associated thrombosis. VTE risk factors, which varied by age, included presence of a central line, major infection, surgery, or trauma. While most VTEs in pediatric patients are expected to be central-line related, in the EINSTEIN-Jr trial only 25.2% of VTEs were central line–associated. The study evaluated symptomatic recurrent VTE (primary efficacy outcome) and clinically relevant bleeding (safety outcome). No significant difference was found between treatment groups in efficacy or safety outcomes, and there were no treatment-related deaths. While the trial was not powered to assess noninferiority due to low incidence of VTE in pediatrics, the absolute number of symptomatic recurrent VTEs was lower in the rivaroxaban group compared with the standard-care group (1% vs 3%). The investigators concluded that rivaroxaban is similarly efficacious and safe in children as compared with adults. FDA approval of rivaroxaban in pediatrics is expected given the trial’s favorable results. Clinicians may wish to consider whether the studied population is comparable with their own patients because the trial had a lower percentage of line-associated VTE than previously reported in the pediatric population.

Multiple clinical trials evaluating the efficacy and safety of other DOACs in pediatric patients are currently underway (Appendix Table).^12-14 Apixaban and edoxaban have active multicenter, randomized, open-label clinical trials recruiting patients up to age 17 who have imaging-confirmed acute VTE. A similar trial for dabigatran has recently completed recruitment. Outcome measures include recurrent VTE, VTE-related mortality, and major or clinically relevant non-major bleeding. Like EINSTEIN-Jr, patients in the dabigatran and edoxaban trials were treated with parenteral therapy for at least 5 days prior to randomization.^12,14 In the apixaban trial, participants can be randomized without initial parenteral treatment.¹³ Betrixaban, the newest DOAC approved in adults, does not currently have any open pediatric trials.

Lack of approved reversal agents may initially limit DOAC use in children. An open-label study examining idarucizumab safety has completed enrollment, but it has not yet published results.¹⁵ To date, there are no pediatric clinical trials examining andexanet alpha. Future work will need to establish efficacy and safety of reversal agents in pediatrics.

DOACs have not been adequately studied in populations of patients with comorbidities, such as liver disease, renal disease, altered enteral absorption, and BMI higher than 40. Physiologic differences in children with cancer and in neonates merit further evaluation of DOAC safety and efficacy. While ongoing trials established weight-based dosing regimens for children, longitudinal studies will need to ensure adequate anticoagulation, especially in the populations listed here.

The safety outcomes in most DOAC studies include clinically relevant bleeding and VTE-related mortality. These outcomes are much less common in pediatric patients than they are in adults, and future studies may need to expand safety outcomes to those more frequently seen in children. Primary and secondary endpoint variability in pediatric DOAC clinical trials presents challenges interpreting and comparing study results.

VTE is an increasingly common complication in hospitalized children contributing to significant morbidity.¹ For decades, the only treatment options have been UFH, LMWH, or warfarin. DOACs offer many advantages compared with standard anticoagulation options. The only clinical trial evaluating efficacy and safety of DOACs published to date demonstrates that pediatric patients taking rivaroxaban have outcomes similar to those of patients receiving standard care. It is expected that DOACs will gain FDA approval for treatment of VTE in pediatric patients in the near future; therefore, hospitalists should understand indications for use of these medications.

Health systems around the world have been called upon to expand acute care capacity to manage the current and projected surge of adults with COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).¹ There has been mixed guidance on how pediatric facilities should consolidate and coordinate pediatric care in a way that optimizes the capacity of hospital beds, staff, and supplies, such as ventilators and medications, for both adults and children in a community.² Furthermore, if and how these pediatric facilities should expand capacity to care for adult patients safely is uncertain.

For the last 5 years, both Boston Children’s Hospital and Cincinnati Children’s Hospital Medical Center have been caring for specific adult populations in free-standing pediatric hospitals because of the increasing prevalence of young adults with rare, complex, and historically fatal conditions (eg, chromosomal abnormalities). In the past, low life expectancies for children with such conditions contributed to the evolution of specialized care in pediatric health systems that often does not exist in adult health systems. Our teams in Boston and Cincinnati have gained insight into the multifaceted infrastructure and teams necessary to provide safe care for adults hospitalized in a pediatric setting.

In this perspective piece, we will highlight important principles that pediatric facilities and providers should prioritize if they anticipate caring for hospitalized adults during this pandemic. Designing and implementing an adult care model requires iteratively addressing the following key areas: development of a multistakeholder team, system readiness for intensive care unit (ICU) care of adults, institutional situation awareness, scope of practice, staffing considerations, patient safety, and patient populations and special considerations (eg, adults with chronic conditions of childhood onset). With these areas in mind, pediatric facilities should then consider whether they have the capacity to manage hospitalized adults.

Providing care for any hospitalized patient requires engagement with many health system stakeholders. By involving key stakeholders early in the planning process for our adult care model, we were able to anticipate potential obstacles when caring for a unique subset of patients and gain support of multidisciplinary partners. For instance, inclusion of bedside and support staff highlighted specific needs, such as nurses with adult training and a revised formulary to include common adult medications (eg, clopidogrel for adults with a drug-eluting stent).

Responding to the surge of hospitalized adult patients will require increasing hospital capacity.³ In pediatric settings, this will require consideration of innovative care models. These care models may include pediatric systems flexing to care for adult patients. We recommend hospital leaders from both pediatric and adult facilities have formal discussions on the best ways for pediatric facilities to respond to serve their local population. Inclusion of other key stakeholders will ensure factors imperative to the safe care of adults will not be missed.

There were three levels of consideration for the use of our local pediatric ICU for these patients. First, our institutional policies allow care for adults throughout the system, which we describe in more detail later, in the “Scope of Practice” section. Second, our free-standing pediatric hospital ICUs have accreditation for the care of adults. Third, we developed clear guidelines for subspecialists regarding when adults can safely be admitted or transferred to the pediatric ICU.

Responding to a crisis still necessitates establishing a clear care-escalation plan. An initial barrier may be that some systems do not have a pediatric ICU accredited for care of patients above a certain age. During a crisis, however, as hospital volumes and mortalities rise, states may pursue executive orders, as New York State did, that ease these age restrictions.⁴ Otherwise, we recommend a clear transfer plan to an adult ICU or emergency credentialing and privileging of adult intensivists. Both of these options may pose challenges during a pandemic because adult ICUs will likely be full.

Institutional situation awareness for the identification and mitigation of risks inherent in adult care in a pediatric setting is essential for patient safety. Tracking of admitted adult patients via our electronic health record (EHR) occurs daily by an adult care–team member. Our adult care teams partner with physician safety officers and attend daily institutional multidisciplinary safety huddles to create a shared mental model for the care of adult patients. Daily huddle reports include discussion regarding the number of admitted adults, review of illness acuity, consultative advice on management, and contingency planning for potential decompensation.^5,6 This integration into institutional huddles has been instrumental in proactively identifying hospitalized adults who are at risk for clinical decompensation and mitigating those risks.

Should a pediatric system admit adults to new sites or units, we recommend leveraging preexisting patient safety infrastructure similarly to identify and mitigate risks. If possible, any institutional communication about adult patients should involve adult-trained staff. Mechanisms for tracking patients will depend on local EHRs but are important to guide regular check-ins with providers caring for those patients.

Multiple levels of regulation affect a provider’s scope of practice. The most general of these regulations are state guidelines, followed by local institutional policy. Our institutions require consults for older adults—age varies at our specific institutions—by our adult-care team for assessment of risk and comanagement of adult-specific comorbidities. Additionally, we have agreements with our affiliated adult health facilities that allow in-person adult subspecialty consultation.

While state and institutional policies lay the foundation for pediatric systems considering new adult-care models, provider-level considerations are also needed. Often the patient’s age is a primary consideration, but comorbid conditions also affect the provider’s comfort and ability to care for these patients. We urge practitioners to exercise the full range of their capacities, but also to think critically about the ethical scope of one’s practice. As healthcare providers, it is our duty to hold each other accountable, voice concerns, and advocate to increase health system capacity equitably.⁷ It’s paramount that channels of communication, in-person or virtual, be arranged for supportive adult subspecialist consultation.

Med-Peds physicians and advanced practice providers are the foundation of the clinical care provided to adults at our institutions. Our Med-Peds providers practice in both the free-standing pediatric hospital and an affiliated adult health system. They offer expertise in adult clinical care and navigate between pediatric and adult systems when the need arises (eg, adult requiring urgent intervention for an acute myocardial infarction). Adult competencies of other staff must be addressed. For example, our cardiac ICUs include nurses with adult clinical care experience because critically ill adults with congenital heart disease are admitted. Advanced Care Life Support (ACLS) training is also required for staff caring for adults throughout the hospital.

There are many ways, even during a crisis, to develop an adult care model in a pediatric setting. Depending on workforce availability, internal medicine, Med-Peds, family medicine, critical care, and emergency medicine physicians could serve on either a primary service or as a consultant to support pediatrics-trained providers in caring for adults should the patient volume and acuity require staffing restructuring. Adult subspecialty access must be addressed. Telehealth may play a significant role in extending clinicians in all of these clinical roles both during the current crisis but also in underresourced settings.⁸ A clear process and indication for emergency or temporary credentialing and privileging necessitates understanding and addressing such challenges early. Training in adult care, or lack thereof, for other staff, such as nurses and respiratory therapists, is also crucial to consider.

Adults are more likely than children to have comorbidities and clinical deterioration while hospitalized. At our institutions, when a rapid response team is called for an adult patient, an adult care–team provider responds to aid in clinical management and determines the appropriate care setting. Additionally, given that the incidence of coronary artery disease increases starting at age 35 years,⁹ our systems have developed procedures for managing time-sensitive conditions seen more commonly in adults, such as acute myocardial infarction, stroke, and pulmonary embolism. Despite simulation training for pediatric providers and staff, it is clear that implementing these procedures is highly dependent on involvement of the adult care team.

With the urgency of implementation, pediatric systems should consider increasing the number of providers and staff with ACLS training, especially for rapid response and code teams. Many pediatric systems may need to evaluate how their code carts are stocked and ensure they are equipped with appropriate medication dosages and sizes of supplies. Emergent and accessible adult care will be needed, especially for issues with time-to-intervention criteria like acute myocardial infarction and stroke. Hospitalized adults with COVID-19 may also have a higher incidence of arrhythmia, cardiac ischemia, and stroke.¹⁰ Consider proactively simulating common COVID-19–related scenarios to build interdisciplinary teamwork in emergency scenarios. Interhospital agreements and pathways exist for sharing medications. Outreach to pharmacies may be indicated to ensure accessibility for medications not commonly found in pediatric systems.

Our children’s hospitals care for certain adult populations with chronic conditions of childhood origin because of the availability of subspecialty clinical expertise. Our adult care team aids in contingency planning to help determine place of admission (adult vs pediatric hospital) depending on patient clinical needs and system expertise. For instance, an adult with congenital heart disease may have two cardiologists—one for congenital heart disease and one for coronary artery disease. Patients with an acute issue such as new-onset arrhythmia may be admitted to our pediatric hospital; however, for a stroke they would be admitted to the adult hospital.

While important and tempting to address this issue first, creating criteria to determine which patient population to admit should be a last consideration during a pandemic. Consider if the decision to admit should be determined based on COVID-19 infection status. From there, types of conditions thought to be within the purview of pediatric practice can be considered. These include basic infectious diseases pathology (eg, skin/soft-tissue infections and pyelonephritis) and chronic conditions of childhood origin (eg, cystic fibrosis, diabetes, and inflammatory bowel disease), which have specialty providers who could work across an extended age range. Conditions potentially more challenging to safely care for in pediatric facilities include acute cardiac conditions (eg, angina, acute coronary syndrome, and arrhythmias), alcohol withdrawal, end-stage liver or kidney disease, and gastrointestinal bleeds. Considerations need to be made for research protocols and novel therapies only available at adult institutions. Through this whole process, it is especially crucial to note care equity and ensure that all patients have access to the highest attainable care possible.

Policymakers at pediatric facilities should think critically about their institution’s capacity to manage adults. In some circumstances, the decision might be to not admit adult patients based on the factors discussed in this paper or other contextual factors of the local healthcare systems. Our role in providing care for adults in pediatric hospitals involves not only ensuring age-appropriate care, but also in supporting patients and other healthcare providers to navigate a fragmented health system. Our adult-care models required building relationships between pediatric and adult health systems. Building these relationships in the setting of crisis can strengthen health systems and healthcare communities beyond the era of COVID-19. Because it’s promoted enhanced collaboration between pediatric and adult facilities, COVID-19 can be a platform to build a better system to support our already vulnerable young adults with chronic conditions of childhood origin for years to come.

Health systems around the world have been called upon to expand acute care capacity to manage the current and projected surge of adults with COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).¹ There has been mixed guidance on how pediatric facilities should consolidate and coordinate pediatric care in a way that optimizes the capacity of hospital beds, staff, and supplies, such as ventilators and medications, for both adults and children in a community.² Furthermore, if and how these pediatric facilities should expand capacity to care for adult patients safely is uncertain.

For the last 5 years, both Boston Children’s Hospital and Cincinnati Children’s Hospital Medical Center have been caring for specific adult populations in free-standing pediatric hospitals because of the increasing prevalence of young adults with rare, complex, and historically fatal conditions (eg, chromosomal abnormalities). In the past, low life expectancies for children with such conditions contributed to the evolution of specialized care in pediatric health systems that often does not exist in adult health systems. Our teams in Boston and Cincinnati have gained insight into the multifaceted infrastructure and teams necessary to provide safe care for adults hospitalized in a pediatric setting.

In this perspective piece, we will highlight important principles that pediatric facilities and providers should prioritize if they anticipate caring for hospitalized adults during this pandemic. Designing and implementing an adult care model requires iteratively addressing the following key areas: development of a multistakeholder team, system readiness for intensive care unit (ICU) care of adults, institutional situation awareness, scope of practice, staffing considerations, patient safety, and patient populations and special considerations (eg, adults with chronic conditions of childhood onset). With these areas in mind, pediatric facilities should then consider whether they have the capacity to manage hospitalized adults.

Providing care for any hospitalized patient requires engagement with many health system stakeholders. By involving key stakeholders early in the planning process for our adult care model, we were able to anticipate potential obstacles when caring for a unique subset of patients and gain support of multidisciplinary partners. For instance, inclusion of bedside and support staff highlighted specific needs, such as nurses with adult training and a revised formulary to include common adult medications (eg, clopidogrel for adults with a drug-eluting stent).

Responding to the surge of hospitalized adult patients will require increasing hospital capacity.³ In pediatric settings, this will require consideration of innovative care models. These care models may include pediatric systems flexing to care for adult patients. We recommend hospital leaders from both pediatric and adult facilities have formal discussions on the best ways for pediatric facilities to respond to serve their local population. Inclusion of other key stakeholders will ensure factors imperative to the safe care of adults will not be missed.

There were three levels of consideration for the use of our local pediatric ICU for these patients. First, our institutional policies allow care for adults throughout the system, which we describe in more detail later, in the “Scope of Practice” section. Second, our free-standing pediatric hospital ICUs have accreditation for the care of adults. Third, we developed clear guidelines for subspecialists regarding when adults can safely be admitted or transferred to the pediatric ICU.

Responding to a crisis still necessitates establishing a clear care-escalation plan. An initial barrier may be that some systems do not have a pediatric ICU accredited for care of patients above a certain age. During a crisis, however, as hospital volumes and mortalities rise, states may pursue executive orders, as New York State did, that ease these age restrictions.⁴ Otherwise, we recommend a clear transfer plan to an adult ICU or emergency credentialing and privileging of adult intensivists. Both of these options may pose challenges during a pandemic because adult ICUs will likely be full.

Institutional situation awareness for the identification and mitigation of risks inherent in adult care in a pediatric setting is essential for patient safety. Tracking of admitted adult patients via our electronic health record (EHR) occurs daily by an adult care–team member. Our adult care teams partner with physician safety officers and attend daily institutional multidisciplinary safety huddles to create a shared mental model for the care of adult patients. Daily huddle reports include discussion regarding the number of admitted adults, review of illness acuity, consultative advice on management, and contingency planning for potential decompensation.^5,6 This integration into institutional huddles has been instrumental in proactively identifying hospitalized adults who are at risk for clinical decompensation and mitigating those risks.

Should a pediatric system admit adults to new sites or units, we recommend leveraging preexisting patient safety infrastructure similarly to identify and mitigate risks. If possible, any institutional communication about adult patients should involve adult-trained staff. Mechanisms for tracking patients will depend on local EHRs but are important to guide regular check-ins with providers caring for those patients.

Multiple levels of regulation affect a provider’s scope of practice. The most general of these regulations are state guidelines, followed by local institutional policy. Our institutions require consults for older adults—age varies at our specific institutions—by our adult-care team for assessment of risk and comanagement of adult-specific comorbidities. Additionally, we have agreements with our affiliated adult health facilities that allow in-person adult subspecialty consultation.

While state and institutional policies lay the foundation for pediatric systems considering new adult-care models, provider-level considerations are also needed. Often the patient’s age is a primary consideration, but comorbid conditions also affect the provider’s comfort and ability to care for these patients. We urge practitioners to exercise the full range of their capacities, but also to think critically about the ethical scope of one’s practice. As healthcare providers, it is our duty to hold each other accountable, voice concerns, and advocate to increase health system capacity equitably.⁷ It’s paramount that channels of communication, in-person or virtual, be arranged for supportive adult subspecialist consultation.

Med-Peds physicians and advanced practice providers are the foundation of the clinical care provided to adults at our institutions. Our Med-Peds providers practice in both the free-standing pediatric hospital and an affiliated adult health system. They offer expertise in adult clinical care and navigate between pediatric and adult systems when the need arises (eg, adult requiring urgent intervention for an acute myocardial infarction). Adult competencies of other staff must be addressed. For example, our cardiac ICUs include nurses with adult clinical care experience because critically ill adults with congenital heart disease are admitted. Advanced Care Life Support (ACLS) training is also required for staff caring for adults throughout the hospital.

There are many ways, even during a crisis, to develop an adult care model in a pediatric setting. Depending on workforce availability, internal medicine, Med-Peds, family medicine, critical care, and emergency medicine physicians could serve on either a primary service or as a consultant to support pediatrics-trained providers in caring for adults should the patient volume and acuity require staffing restructuring. Adult subspecialty access must be addressed. Telehealth may play a significant role in extending clinicians in all of these clinical roles both during the current crisis but also in underresourced settings.⁸ A clear process and indication for emergency or temporary credentialing and privileging necessitates understanding and addressing such challenges early. Training in adult care, or lack thereof, for other staff, such as nurses and respiratory therapists, is also crucial to consider.

Adults are more likely than children to have comorbidities and clinical deterioration while hospitalized. At our institutions, when a rapid response team is called for an adult patient, an adult care–team provider responds to aid in clinical management and determines the appropriate care setting. Additionally, given that the incidence of coronary artery disease increases starting at age 35 years,⁹ our systems have developed procedures for managing time-sensitive conditions seen more commonly in adults, such as acute myocardial infarction, stroke, and pulmonary embolism. Despite simulation training for pediatric providers and staff, it is clear that implementing these procedures is highly dependent on involvement of the adult care team.

With the urgency of implementation, pediatric systems should consider increasing the number of providers and staff with ACLS training, especially for rapid response and code teams. Many pediatric systems may need to evaluate how their code carts are stocked and ensure they are equipped with appropriate medication dosages and sizes of supplies. Emergent and accessible adult care will be needed, especially for issues with time-to-intervention criteria like acute myocardial infarction and stroke. Hospitalized adults with COVID-19 may also have a higher incidence of arrhythmia, cardiac ischemia, and stroke.¹⁰ Consider proactively simulating common COVID-19–related scenarios to build interdisciplinary teamwork in emergency scenarios. Interhospital agreements and pathways exist for sharing medications. Outreach to pharmacies may be indicated to ensure accessibility for medications not commonly found in pediatric systems.

Our children’s hospitals care for certain adult populations with chronic conditions of childhood origin because of the availability of subspecialty clinical expertise. Our adult care team aids in contingency planning to help determine place of admission (adult vs pediatric hospital) depending on patient clinical needs and system expertise. For instance, an adult with congenital heart disease may have two cardiologists—one for congenital heart disease and one for coronary artery disease. Patients with an acute issue such as new-onset arrhythmia may be admitted to our pediatric hospital; however, for a stroke they would be admitted to the adult hospital.

While important and tempting to address this issue first, creating criteria to determine which patient population to admit should be a last consideration during a pandemic. Consider if the decision to admit should be determined based on COVID-19 infection status. From there, types of conditions thought to be within the purview of pediatric practice can be considered. These include basic infectious diseases pathology (eg, skin/soft-tissue infections and pyelonephritis) and chronic conditions of childhood origin (eg, cystic fibrosis, diabetes, and inflammatory bowel disease), which have specialty providers who could work across an extended age range. Conditions potentially more challenging to safely care for in pediatric facilities include acute cardiac conditions (eg, angina, acute coronary syndrome, and arrhythmias), alcohol withdrawal, end-stage liver or kidney disease, and gastrointestinal bleeds. Considerations need to be made for research protocols and novel therapies only available at adult institutions. Through this whole process, it is especially crucial to note care equity and ensure that all patients have access to the highest attainable care possible.

Policymakers at pediatric facilities should think critically about their institution’s capacity to manage adults. In some circumstances, the decision might be to not admit adult patients based on the factors discussed in this paper or other contextual factors of the local healthcare systems. Our role in providing care for adults in pediatric hospitals involves not only ensuring age-appropriate care, but also in supporting patients and other healthcare providers to navigate a fragmented health system. Our adult-care models required building relationships between pediatric and adult health systems. Building these relationships in the setting of crisis can strengthen health systems and healthcare communities beyond the era of COVID-19. Because it’s promoted enhanced collaboration between pediatric and adult facilities, COVID-19 can be a platform to build a better system to support our already vulnerable young adults with chronic conditions of childhood origin for years to come.

Health systems around the world have been called upon to expand acute care capacity to manage the current and projected surge of adults with COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).¹ There has been mixed guidance on how pediatric facilities should consolidate and coordinate pediatric care in a way that optimizes the capacity of hospital beds, staff, and supplies, such as ventilators and medications, for both adults and children in a community.² Furthermore, if and how these pediatric facilities should expand capacity to care for adult patients safely is uncertain.

For the last 5 years, both Boston Children’s Hospital and Cincinnati Children’s Hospital Medical Center have been caring for specific adult populations in free-standing pediatric hospitals because of the increasing prevalence of young adults with rare, complex, and historically fatal conditions (eg, chromosomal abnormalities). In the past, low life expectancies for children with such conditions contributed to the evolution of specialized care in pediatric health systems that often does not exist in adult health systems. Our teams in Boston and Cincinnati have gained insight into the multifaceted infrastructure and teams necessary to provide safe care for adults hospitalized in a pediatric setting.

In this perspective piece, we will highlight important principles that pediatric facilities and providers should prioritize if they anticipate caring for hospitalized adults during this pandemic. Designing and implementing an adult care model requires iteratively addressing the following key areas: development of a multistakeholder team, system readiness for intensive care unit (ICU) care of adults, institutional situation awareness, scope of practice, staffing considerations, patient safety, and patient populations and special considerations (eg, adults with chronic conditions of childhood onset). With these areas in mind, pediatric facilities should then consider whether they have the capacity to manage hospitalized adults.

Providing care for any hospitalized patient requires engagement with many health system stakeholders. By involving key stakeholders early in the planning process for our adult care model, we were able to anticipate potential obstacles when caring for a unique subset of patients and gain support of multidisciplinary partners. For instance, inclusion of bedside and support staff highlighted specific needs, such as nurses with adult training and a revised formulary to include common adult medications (eg, clopidogrel for adults with a drug-eluting stent).

Responding to the surge of hospitalized adult patients will require increasing hospital capacity.³ In pediatric settings, this will require consideration of innovative care models. These care models may include pediatric systems flexing to care for adult patients. We recommend hospital leaders from both pediatric and adult facilities have formal discussions on the best ways for pediatric facilities to respond to serve their local population. Inclusion of other key stakeholders will ensure factors imperative to the safe care of adults will not be missed.

There were three levels of consideration for the use of our local pediatric ICU for these patients. First, our institutional policies allow care for adults throughout the system, which we describe in more detail later, in the “Scope of Practice” section. Second, our free-standing pediatric hospital ICUs have accreditation for the care of adults. Third, we developed clear guidelines for subspecialists regarding when adults can safely be admitted or transferred to the pediatric ICU.

Responding to a crisis still necessitates establishing a clear care-escalation plan. An initial barrier may be that some systems do not have a pediatric ICU accredited for care of patients above a certain age. During a crisis, however, as hospital volumes and mortalities rise, states may pursue executive orders, as New York State did, that ease these age restrictions.⁴ Otherwise, we recommend a clear transfer plan to an adult ICU or emergency credentialing and privileging of adult intensivists. Both of these options may pose challenges during a pandemic because adult ICUs will likely be full.

Institutional situation awareness for the identification and mitigation of risks inherent in adult care in a pediatric setting is essential for patient safety. Tracking of admitted adult patients via our electronic health record (EHR) occurs daily by an adult care–team member. Our adult care teams partner with physician safety officers and attend daily institutional multidisciplinary safety huddles to create a shared mental model for the care of adult patients. Daily huddle reports include discussion regarding the number of admitted adults, review of illness acuity, consultative advice on management, and contingency planning for potential decompensation.^5,6 This integration into institutional huddles has been instrumental in proactively identifying hospitalized adults who are at risk for clinical decompensation and mitigating those risks.

Should a pediatric system admit adults to new sites or units, we recommend leveraging preexisting patient safety infrastructure similarly to identify and mitigate risks. If possible, any institutional communication about adult patients should involve adult-trained staff. Mechanisms for tracking patients will depend on local EHRs but are important to guide regular check-ins with providers caring for those patients.

Multiple levels of regulation affect a provider’s scope of practice. The most general of these regulations are state guidelines, followed by local institutional policy. Our institutions require consults for older adults—age varies at our specific institutions—by our adult-care team for assessment of risk and comanagement of adult-specific comorbidities. Additionally, we have agreements with our affiliated adult health facilities that allow in-person adult subspecialty consultation.

While state and institutional policies lay the foundation for pediatric systems considering new adult-care models, provider-level considerations are also needed. Often the patient’s age is a primary consideration, but comorbid conditions also affect the provider’s comfort and ability to care for these patients. We urge practitioners to exercise the full range of their capacities, but also to think critically about the ethical scope of one’s practice. As healthcare providers, it is our duty to hold each other accountable, voice concerns, and advocate to increase health system capacity equitably.⁷ It’s paramount that channels of communication, in-person or virtual, be arranged for supportive adult subspecialist consultation.

Med-Peds physicians and advanced practice providers are the foundation of the clinical care provided to adults at our institutions. Our Med-Peds providers practice in both the free-standing pediatric hospital and an affiliated adult health system. They offer expertise in adult clinical care and navigate between pediatric and adult systems when the need arises (eg, adult requiring urgent intervention for an acute myocardial infarction). Adult competencies of other staff must be addressed. For example, our cardiac ICUs include nurses with adult clinical care experience because critically ill adults with congenital heart disease are admitted. Advanced Care Life Support (ACLS) training is also required for staff caring for adults throughout the hospital.

There are many ways, even during a crisis, to develop an adult care model in a pediatric setting. Depending on workforce availability, internal medicine, Med-Peds, family medicine, critical care, and emergency medicine physicians could serve on either a primary service or as a consultant to support pediatrics-trained providers in caring for adults should the patient volume and acuity require staffing restructuring. Adult subspecialty access must be addressed. Telehealth may play a significant role in extending clinicians in all of these clinical roles both during the current crisis but also in underresourced settings.⁸ A clear process and indication for emergency or temporary credentialing and privileging necessitates understanding and addressing such challenges early. Training in adult care, or lack thereof, for other staff, such as nurses and respiratory therapists, is also crucial to consider.

Adults are more likely than children to have comorbidities and clinical deterioration while hospitalized. At our institutions, when a rapid response team is called for an adult patient, an adult care–team provider responds to aid in clinical management and determines the appropriate care setting. Additionally, given that the incidence of coronary artery disease increases starting at age 35 years,⁹ our systems have developed procedures for managing time-sensitive conditions seen more commonly in adults, such as acute myocardial infarction, stroke, and pulmonary embolism. Despite simulation training for pediatric providers and staff, it is clear that implementing these procedures is highly dependent on involvement of the adult care team.

With the urgency of implementation, pediatric systems should consider increasing the number of providers and staff with ACLS training, especially for rapid response and code teams. Many pediatric systems may need to evaluate how their code carts are stocked and ensure they are equipped with appropriate medication dosages and sizes of supplies. Emergent and accessible adult care will be needed, especially for issues with time-to-intervention criteria like acute myocardial infarction and stroke. Hospitalized adults with COVID-19 may also have a higher incidence of arrhythmia, cardiac ischemia, and stroke.¹⁰ Consider proactively simulating common COVID-19–related scenarios to build interdisciplinary teamwork in emergency scenarios. Interhospital agreements and pathways exist for sharing medications. Outreach to pharmacies may be indicated to ensure accessibility for medications not commonly found in pediatric systems.

Our children’s hospitals care for certain adult populations with chronic conditions of childhood origin because of the availability of subspecialty clinical expertise. Our adult care team aids in contingency planning to help determine place of admission (adult vs pediatric hospital) depending on patient clinical needs and system expertise. For instance, an adult with congenital heart disease may have two cardiologists—one for congenital heart disease and one for coronary artery disease. Patients with an acute issue such as new-onset arrhythmia may be admitted to our pediatric hospital; however, for a stroke they would be admitted to the adult hospital.

While important and tempting to address this issue first, creating criteria to determine which patient population to admit should be a last consideration during a pandemic. Consider if the decision to admit should be determined based on COVID-19 infection status. From there, types of conditions thought to be within the purview of pediatric practice can be considered. These include basic infectious diseases pathology (eg, skin/soft-tissue infections and pyelonephritis) and chronic conditions of childhood origin (eg, cystic fibrosis, diabetes, and inflammatory bowel disease), which have specialty providers who could work across an extended age range. Conditions potentially more challenging to safely care for in pediatric facilities include acute cardiac conditions (eg, angina, acute coronary syndrome, and arrhythmias), alcohol withdrawal, end-stage liver or kidney disease, and gastrointestinal bleeds. Considerations need to be made for research protocols and novel therapies only available at adult institutions. Through this whole process, it is especially crucial to note care equity and ensure that all patients have access to the highest attainable care possible.

Policymakers at pediatric facilities should think critically about their institution’s capacity to manage adults. In some circumstances, the decision might be to not admit adult patients based on the factors discussed in this paper or other contextual factors of the local healthcare systems. Our role in providing care for adults in pediatric hospitals involves not only ensuring age-appropriate care, but also in supporting patients and other healthcare providers to navigate a fragmented health system. Our adult-care models required building relationships between pediatric and adult health systems. Building these relationships in the setting of crisis can strengthen health systems and healthcare communities beyond the era of COVID-19. Because it’s promoted enhanced collaboration between pediatric and adult facilities, COVID-19 can be a platform to build a better system to support our already vulnerable young adults with chronic conditions of childhood origin for years to come.

Acute pancreatitis (AP) is the most common gastrointestinal discharge diagnosis in the United States, with a mortality rate of 1%-5%.¹ Recent data demonstrate increasing AP-related admissions, making AP management of utmost importance to hospitalists.¹ The American Gastroenterological Association (AGA) guideline specifically addresses AP management in the initial 48-72 hours of admission, during which management decisions can alter disease course and length of stay. AP requires two of the following three criteria for diagnosis: characteristic abdominal pain, elevation of lipase or amylase ≥3 times the upper limit of normal, and/or radiographic evidence of pancreatitis on cross-sectional imaging. The guideline provides eight recommendations, which we consolidated to highlight practice changing recommendations: fluids, nutrition, management of the most common causes, and prophylactic antibiotics.^2,3

KEY RECOMMENDATIONS FOR THE HOSPITALIST

Fluids

Recommendation 1. In patients with AP, use goal-directed isotonic crystalloids for fluid management (conditional recommendation, very low-quality evidence).

The guideline emphasizes goal-directed fluid management despite low-quality, heterogeneous evidence and does not recommend Ringer’s lactate over normal saline. “Goal-directed” fluid management involves the use of crystalloid infusions titrated to improve physiologic and biochemical markers, but no target volume is specified by the guideline. Frequent reassessments should look for signs of volume overload, the primary risk of harm with fluid therapy. Despite failure to reduce mortality or morbidities such as pancreatic necrosis or persistent multi-organ failure, the AGA cites the mortality benefit of goal-directed therapy in sepsis as justification for this approach in AP, given the similar physiologic abnormalities.

Nutrition

Recommendation 2. Begin feeding early in patients with AP regardless of predicted severity. If oral nutrition is not tolerated, enteral feeding with either a nasogastric or nasojejunal tube is preferred to parenteral nutrition (strong recommendation, moderate-quality evidence).

Early feeding (ie, within 24 hours) is recommended regardless of AP severity. This represents a change from prior practices of bowel rest, theorized to prevent continued stimulation of an inflamed pancreas. Although early feeding has not been linked to improved mortality, it has demonstrated lower rates of multi-organ failure and infected pancreatic necrosis, possibly due to maintenance of the gut mucosal barrier and reduced bacterial translocation. When oral feeding is not tolerated, enteral nutrition is preferred over parenteral nutrition due to less risks. The preferred dietary composition guidance for patients with persistent pain or ileus is not addressed.

Management of the Most Common Causes of AP in Adults

Recommendation 3. Patients with mild acute biliary pancreatitis should have cholecystectomy during the initial admission (strong recommendation, moderate-quality evidence).

All patients with suspected biliary pancreatitis should receive a surgical consultation for cholecystectomy during the index admission. At the time of the guideline release, only one trial was available to support the recommendation of early cholecystectomy; however, newer studies similarly support cholecystectomy during index admission by demonstrating reductions in composite outcomes of mortality and gallstone-related complications, readmission for pancreatitis, and other pancreatobiliary complications.⁴ A Cochrane review included in the guideline found no differences in complication rates even in patients with severe biliary pancreatitis. In the absence of cholangitis, urgent endoscopic retrograde cholangiography (ERCP) is not indicated as most stones causing biliary pancreatitis pass spontaneously.

Recommendation 4. In patients with acute alcoholic pancreatitis, brief alcohol intervention should occur during admission (strong recommendation, moderate-quality evidence).

Ongoing alcohol consumption is a risk factor for recurrent acute and chronic pancreatitis. Only one trial assessed the impact of inpatient alcohol cessation counseling on recurrent AP, noting a trend toward reduced readmissions.⁵ However, indirect evidence from similar interventions in ambulatory settings demonstrates reductions in alcohol intake, leading to the AGA recommendation for inpatients with alcohol-induced AP.³

Antibiotics

Recommendation 5. Avoid empiric antibiotics in patients with AP who otherwise lack an indication, regardless of predicted severity (conditional recommendation, low-quality evidence).

Since 2002, well performed trials have consistently failed to demonstrate improvement in outcomes such as multi-organ failure or length of stay with use of prophylactic antibiotics for AP, even severe AP and pancreatic necrosis. Therefore, the AGA recommends against prophylactic antibiotics in initial management of AP regardless of disease severity. Lack of blinding in the majority of trial designs conducted before 2002 contributed to the overall assessment of low-quality evidence. The guideline does not address acute biliary pancreatitis with cholangitis, for which antibiotics and ERCP for decompression are critical.

CRITIQUE

The AGA Institute supported this guideline development and employed the rigorous and standardized GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. This approach allowed the guideline panel members to account not only for evidence quality, but also the benefits and harms of an intervention and resource utilization. None of the authors had any stated conflicts of interest.

The guideline heavily weighted results from randomized control trials, most of which excluded key populations cared for by hospitalists (eg, patients older than 75 years, with end-stage renal disease). Particular areas where this creates challenges for clinicians and patients alike include goal-directed fluid therapy and when to consider more invasive interventions such as ERCP and early cholecystectomy. For example, patients considered to be poor surgical candidates may benefit from ERCP with biliary sphincterotomy to reduce the risk of recurrent biliary pancreatitis.

Lack of specificity in the guidelines for goal-directed fluid management and enteral feeding regimens makes it challenging to standardize hospitalists’ approach to the early care of patients with AP. Interestingly, the 2013 American College of Gastroenterology (ACG) Guideline for the Management of AP included strong recommendations for the use of Ringer’s lactate and volume targets in the initial management of AP.⁶ Evidence supporting the use of Ringer’s lactate versus normal saline is based largely upon improved inflammatory markers, theoretical potentiation of pancreatic enzyme activation with hypercholemic metabolic acidosis, and small studies demonstrating trends toward improved mortality.⁷ The ACG guideline was released prior to mounting evidence suggesting that goal-directed fluid therapy in sepsis does not improve mortality versus usual care.⁸ The growing uncertainty regarding the efficacy of goal-directed fluids for septic shock, as well limitations of studies on AP, may contribute to the differences between the AGA and ACG recommendations.

Finally, as the guideline covers the initial therapeutic management of AP, no recommendations are made for diagnostic studies such as right upper quadrant ultrasound. This noninvasive and readily available test plays a critical role in evaluating for presence of gallstones and other potential etiologies of abdominal pain.

AREAS IN NEED OF FUTURE STUDY

Additional research is needed to better understand goal-directed fluid therapy with respect to the fluid type, amount, and target outcomes. Similarly, determining the optimal enteral feeding regimens for patients failing oral intake would help clinicians meet the recommendation for early nutrition. Finally, clarification on the roles and timing of endoscopic and surgical procedures for patients with severe biliary pancreatitis, as well as geriatric and medically complex populations, would help hospitalists advocate for a multidisciplinary approach to this common and often serious disease.

Disclosures

The authors have nothing to disclose.

Acute pancreatitis (AP) is the most common gastrointestinal discharge diagnosis in the United States, with a mortality rate of 1%-5%.¹ Recent data demonstrate increasing AP-related admissions, making AP management of utmost importance to hospitalists.¹ The American Gastroenterological Association (AGA) guideline specifically addresses AP management in the initial 48-72 hours of admission, during which management decisions can alter disease course and length of stay. AP requires two of the following three criteria for diagnosis: characteristic abdominal pain, elevation of lipase or amylase ≥3 times the upper limit of normal, and/or radiographic evidence of pancreatitis on cross-sectional imaging. The guideline provides eight recommendations, which we consolidated to highlight practice changing recommendations: fluids, nutrition, management of the most common causes, and prophylactic antibiotics.^2,3

KEY RECOMMENDATIONS FOR THE HOSPITALIST

Fluids

Recommendation 1. In patients with AP, use goal-directed isotonic crystalloids for fluid management (conditional recommendation, very low-quality evidence).

The guideline emphasizes goal-directed fluid management despite low-quality, heterogeneous evidence and does not recommend Ringer’s lactate over normal saline. “Goal-directed” fluid management involves the use of crystalloid infusions titrated to improve physiologic and biochemical markers, but no target volume is specified by the guideline. Frequent reassessments should look for signs of volume overload, the primary risk of harm with fluid therapy. Despite failure to reduce mortality or morbidities such as pancreatic necrosis or persistent multi-organ failure, the AGA cites the mortality benefit of goal-directed therapy in sepsis as justification for this approach in AP, given the similar physiologic abnormalities.

Nutrition

Recommendation 2. Begin feeding early in patients with AP regardless of predicted severity. If oral nutrition is not tolerated, enteral feeding with either a nasogastric or nasojejunal tube is preferred to parenteral nutrition (strong recommendation, moderate-quality evidence).

Early feeding (ie, within 24 hours) is recommended regardless of AP severity. This represents a change from prior practices of bowel rest, theorized to prevent continued stimulation of an inflamed pancreas. Although early feeding has not been linked to improved mortality, it has demonstrated lower rates of multi-organ failure and infected pancreatic necrosis, possibly due to maintenance of the gut mucosal barrier and reduced bacterial translocation. When oral feeding is not tolerated, enteral nutrition is preferred over parenteral nutrition due to less risks. The preferred dietary composition guidance for patients with persistent pain or ileus is not addressed.

Management of the Most Common Causes of AP in Adults

Recommendation 3. Patients with mild acute biliary pancreatitis should have cholecystectomy during the initial admission (strong recommendation, moderate-quality evidence).

All patients with suspected biliary pancreatitis should receive a surgical consultation for cholecystectomy during the index admission. At the time of the guideline release, only one trial was available to support the recommendation of early cholecystectomy; however, newer studies similarly support cholecystectomy during index admission by demonstrating reductions in composite outcomes of mortality and gallstone-related complications, readmission for pancreatitis, and other pancreatobiliary complications.⁴ A Cochrane review included in the guideline found no differences in complication rates even in patients with severe biliary pancreatitis. In the absence of cholangitis, urgent endoscopic retrograde cholangiography (ERCP) is not indicated as most stones causing biliary pancreatitis pass spontaneously.

Recommendation 4. In patients with acute alcoholic pancreatitis, brief alcohol intervention should occur during admission (strong recommendation, moderate-quality evidence).

Ongoing alcohol consumption is a risk factor for recurrent acute and chronic pancreatitis. Only one trial assessed the impact of inpatient alcohol cessation counseling on recurrent AP, noting a trend toward reduced readmissions.⁵ However, indirect evidence from similar interventions in ambulatory settings demonstrates reductions in alcohol intake, leading to the AGA recommendation for inpatients with alcohol-induced AP.³

Antibiotics

Recommendation 5. Avoid empiric antibiotics in patients with AP who otherwise lack an indication, regardless of predicted severity (conditional recommendation, low-quality evidence).

Since 2002, well performed trials have consistently failed to demonstrate improvement in outcomes such as multi-organ failure or length of stay with use of prophylactic antibiotics for AP, even severe AP and pancreatic necrosis. Therefore, the AGA recommends against prophylactic antibiotics in initial management of AP regardless of disease severity. Lack of blinding in the majority of trial designs conducted before 2002 contributed to the overall assessment of low-quality evidence. The guideline does not address acute biliary pancreatitis with cholangitis, for which antibiotics and ERCP for decompression are critical.

CRITIQUE

The AGA Institute supported this guideline development and employed the rigorous and standardized GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. This approach allowed the guideline panel members to account not only for evidence quality, but also the benefits and harms of an intervention and resource utilization. None of the authors had any stated conflicts of interest.

The guideline heavily weighted results from randomized control trials, most of which excluded key populations cared for by hospitalists (eg, patients older than 75 years, with end-stage renal disease). Particular areas where this creates challenges for clinicians and patients alike include goal-directed fluid therapy and when to consider more invasive interventions such as ERCP and early cholecystectomy. For example, patients considered to be poor surgical candidates may benefit from ERCP with biliary sphincterotomy to reduce the risk of recurrent biliary pancreatitis.

Lack of specificity in the guidelines for goal-directed fluid management and enteral feeding regimens makes it challenging to standardize hospitalists’ approach to the early care of patients with AP. Interestingly, the 2013 American College of Gastroenterology (ACG) Guideline for the Management of AP included strong recommendations for the use of Ringer’s lactate and volume targets in the initial management of AP.⁶ Evidence supporting the use of Ringer’s lactate versus normal saline is based largely upon improved inflammatory markers, theoretical potentiation of pancreatic enzyme activation with hypercholemic metabolic acidosis, and small studies demonstrating trends toward improved mortality.⁷ The ACG guideline was released prior to mounting evidence suggesting that goal-directed fluid therapy in sepsis does not improve mortality versus usual care.⁸ The growing uncertainty regarding the efficacy of goal-directed fluids for septic shock, as well limitations of studies on AP, may contribute to the differences between the AGA and ACG recommendations.

Finally, as the guideline covers the initial therapeutic management of AP, no recommendations are made for diagnostic studies such as right upper quadrant ultrasound. This noninvasive and readily available test plays a critical role in evaluating for presence of gallstones and other potential etiologies of abdominal pain.

AREAS IN NEED OF FUTURE STUDY

Additional research is needed to better understand goal-directed fluid therapy with respect to the fluid type, amount, and target outcomes. Similarly, determining the optimal enteral feeding regimens for patients failing oral intake would help clinicians meet the recommendation for early nutrition. Finally, clarification on the roles and timing of endoscopic and surgical procedures for patients with severe biliary pancreatitis, as well as geriatric and medically complex populations, would help hospitalists advocate for a multidisciplinary approach to this common and often serious disease.

Disclosures

The authors have nothing to disclose.

Acute pancreatitis (AP) is the most common gastrointestinal discharge diagnosis in the United States, with a mortality rate of 1%-5%.¹ Recent data demonstrate increasing AP-related admissions, making AP management of utmost importance to hospitalists.¹ The American Gastroenterological Association (AGA) guideline specifically addresses AP management in the initial 48-72 hours of admission, during which management decisions can alter disease course and length of stay. AP requires two of the following three criteria for diagnosis: characteristic abdominal pain, elevation of lipase or amylase ≥3 times the upper limit of normal, and/or radiographic evidence of pancreatitis on cross-sectional imaging. The guideline provides eight recommendations, which we consolidated to highlight practice changing recommendations: fluids, nutrition, management of the most common causes, and prophylactic antibiotics.^2,3

KEY RECOMMENDATIONS FOR THE HOSPITALIST

Fluids

Recommendation 1. In patients with AP, use goal-directed isotonic crystalloids for fluid management (conditional recommendation, very low-quality evidence).

The guideline emphasizes goal-directed fluid management despite low-quality, heterogeneous evidence and does not recommend Ringer’s lactate over normal saline. “Goal-directed” fluid management involves the use of crystalloid infusions titrated to improve physiologic and biochemical markers, but no target volume is specified by the guideline. Frequent reassessments should look for signs of volume overload, the primary risk of harm with fluid therapy. Despite failure to reduce mortality or morbidities such as pancreatic necrosis or persistent multi-organ failure, the AGA cites the mortality benefit of goal-directed therapy in sepsis as justification for this approach in AP, given the similar physiologic abnormalities.

Nutrition

Recommendation 2. Begin feeding early in patients with AP regardless of predicted severity. If oral nutrition is not tolerated, enteral feeding with either a nasogastric or nasojejunal tube is preferred to parenteral nutrition (strong recommendation, moderate-quality evidence).

Early feeding (ie, within 24 hours) is recommended regardless of AP severity. This represents a change from prior practices of bowel rest, theorized to prevent continued stimulation of an inflamed pancreas. Although early feeding has not been linked to improved mortality, it has demonstrated lower rates of multi-organ failure and infected pancreatic necrosis, possibly due to maintenance of the gut mucosal barrier and reduced bacterial translocation. When oral feeding is not tolerated, enteral nutrition is preferred over parenteral nutrition due to less risks. The preferred dietary composition guidance for patients with persistent pain or ileus is not addressed.

Management of the Most Common Causes of AP in Adults

Recommendation 3. Patients with mild acute biliary pancreatitis should have cholecystectomy during the initial admission (strong recommendation, moderate-quality evidence).

All patients with suspected biliary pancreatitis should receive a surgical consultation for cholecystectomy during the index admission. At the time of the guideline release, only one trial was available to support the recommendation of early cholecystectomy; however, newer studies similarly support cholecystectomy during index admission by demonstrating reductions in composite outcomes of mortality and gallstone-related complications, readmission for pancreatitis, and other pancreatobiliary complications.⁴ A Cochrane review included in the guideline found no differences in complication rates even in patients with severe biliary pancreatitis. In the absence of cholangitis, urgent endoscopic retrograde cholangiography (ERCP) is not indicated as most stones causing biliary pancreatitis pass spontaneously.

Recommendation 4. In patients with acute alcoholic pancreatitis, brief alcohol intervention should occur during admission (strong recommendation, moderate-quality evidence).

Ongoing alcohol consumption is a risk factor for recurrent acute and chronic pancreatitis. Only one trial assessed the impact of inpatient alcohol cessation counseling on recurrent AP, noting a trend toward reduced readmissions.⁵ However, indirect evidence from similar interventions in ambulatory settings demonstrates reductions in alcohol intake, leading to the AGA recommendation for inpatients with alcohol-induced AP.³

Antibiotics

Recommendation 5. Avoid empiric antibiotics in patients with AP who otherwise lack an indication, regardless of predicted severity (conditional recommendation, low-quality evidence).

Since 2002, well performed trials have consistently failed to demonstrate improvement in outcomes such as multi-organ failure or length of stay with use of prophylactic antibiotics for AP, even severe AP and pancreatic necrosis. Therefore, the AGA recommends against prophylactic antibiotics in initial management of AP regardless of disease severity. Lack of blinding in the majority of trial designs conducted before 2002 contributed to the overall assessment of low-quality evidence. The guideline does not address acute biliary pancreatitis with cholangitis, for which antibiotics and ERCP for decompression are critical.

CRITIQUE

The AGA Institute supported this guideline development and employed the rigorous and standardized GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. This approach allowed the guideline panel members to account not only for evidence quality, but also the benefits and harms of an intervention and resource utilization. None of the authors had any stated conflicts of interest.

The guideline heavily weighted results from randomized control trials, most of which excluded key populations cared for by hospitalists (eg, patients older than 75 years, with end-stage renal disease). Particular areas where this creates challenges for clinicians and patients alike include goal-directed fluid therapy and when to consider more invasive interventions such as ERCP and early cholecystectomy. For example, patients considered to be poor surgical candidates may benefit from ERCP with biliary sphincterotomy to reduce the risk of recurrent biliary pancreatitis.

Lack of specificity in the guidelines for goal-directed fluid management and enteral feeding regimens makes it challenging to standardize hospitalists’ approach to the early care of patients with AP. Interestingly, the 2013 American College of Gastroenterology (ACG) Guideline for the Management of AP included strong recommendations for the use of Ringer’s lactate and volume targets in the initial management of AP.⁶ Evidence supporting the use of Ringer’s lactate versus normal saline is based largely upon improved inflammatory markers, theoretical potentiation of pancreatic enzyme activation with hypercholemic metabolic acidosis, and small studies demonstrating trends toward improved mortality.⁷ The ACG guideline was released prior to mounting evidence suggesting that goal-directed fluid therapy in sepsis does not improve mortality versus usual care.⁸ The growing uncertainty regarding the efficacy of goal-directed fluids for septic shock, as well limitations of studies on AP, may contribute to the differences between the AGA and ACG recommendations.

Finally, as the guideline covers the initial therapeutic management of AP, no recommendations are made for diagnostic studies such as right upper quadrant ultrasound. This noninvasive and readily available test plays a critical role in evaluating for presence of gallstones and other potential etiologies of abdominal pain.

AREAS IN NEED OF FUTURE STUDY

Additional research is needed to better understand goal-directed fluid therapy with respect to the fluid type, amount, and target outcomes. Similarly, determining the optimal enteral feeding regimens for patients failing oral intake would help clinicians meet the recommendation for early nutrition. Finally, clarification on the roles and timing of endoscopic and surgical procedures for patients with severe biliary pancreatitis, as well as geriatric and medically complex populations, would help hospitalists advocate for a multidisciplinary approach to this common and often serious disease.

Disclosures

The authors have nothing to disclose.

The transition from hospital to home can be overwhelming for caregivers.¹ Stress of hospitalization coupled with the expectation of families to execute postdischarge care plans make understandable discharge communication critical. Communication failures, inadequate education, absence of caregiver confidence, and lack of clarity regarding care plans may prohibit smooth transitions and lead to adverse postdischarge outcomes.^2-4

Health literacy plays a pivotal role in caregivers’ capacity to navigate the healthcare system, comprehend, and execute care plans. An estimated 90 million Americans have limited health literacy that may negatively impact the provision of safe and quality care^5,6 and be a risk factor for poor outcomes, including increased emergency department (ED) utilization and readmission rates.^7-9 Readability strongly influences the effectiveness of written materials.¹⁰ However, written medical information for patients and families are frequently between the 10^th and 12^th grade reading levels; more than 75% of all pediatric health information is written at or above 10^th grade reading level.¹¹ Government agencies recommend between a 6^th and 8^th grade reading level, for written material;^5,12,13 written discharge instructions have been identified as an important quality metric for hospital-to-home transitions.^14-16

At our center, we found that discharge instructions were commonly written at high reading levels and often incomplete.¹⁷ Poor discharge instructions may contribute to increased readmission rates and unnecessary ED visits.^9,18 Our global aim targeted improved health-literate written information, including understandability and completeness.

Our specific aim was to increase the percentage of discharge instructions written at or below the 7th grade level for hospital medicine (HM) patients on a community hospital pediatric unit from 13% to 80% in 6 months.

Context

The improvement work took place at a 42-bed inpatient pediatric unit at a community satellite of our large, urban, academic hospital. The unit is staffed by medical providers including attendings, fellows, nurse practitioners (NPs), and senior pediatric residents, and had more than 1000 HM discharges in fiscal year 2016. Children with common general pediatric diagnoses are admitted to this service; postsurgical patients are not admitted primarily to the HM service. In Cincinnati, the neighborhood-level high school drop-out rates are as high as 64%.¹⁹ Discharge instructions are written by medical providers in the electronic health record (EHR). A printed copy is given to families and verbally reviewed by a bedside nurse prior to discharge. Quality improvement (QI) efforts focused on discharge instructions were ignited by a prior review of 200 discharge instructions that showed they were difficult to read (median reading level of 10^th grade), poorly understandable (36% of instructions met the threshold of understandability as measured by the Patient Education Materials Assessment Tool²⁰) and were missing key elements of information.¹⁷

Improvement Team

The improvement team consisted of 4 pediatric hospitalists, 2 NPs, 1 nurse educator with health literacy expertise, 1 pediatric resident, 1 fourth-year medical student, 1 QI consultant, and 2 parents who had first-hand experience on the HM service. The improvement team observed the discharge process, including roles of the provider, nurse and family, outlined a process map, and created a modified failure mode and effect analysis.²¹ Prior to our work, discharge instructions written by providers often occurred as a last step, and the content was created as free text or from nonstandardized templates. Key drivers that informed interventions were determined and revised over time (Figure 1). The study was reviewed by our institutional review board and deemed not human subjects research.

Improvement Activities

Key drivers were identified, and interventions were executed using Plan-Do Study-Act cycles.²² The key drivers thought to be critical for the success of the QI efforts were family engagement; standardization of discharge instructions; medical staff engagement; and audit and feedback of data. The corresponding interventions were as follows:

Family Engagement

Understanding the discharge information families desired. Prior to testing, 10 families admitted to the HM service were asked about the discharge experience. We asked families about information they wanted in written discharge instructions: 1) reasons to call your primary doctor or return to the hospital; 2) when to see your primary doctor for a follow-up visit; 3) the phone number to reach your child’s doctor; 4) more information about why your child was admitted; 5) information about new medications; and 6) what to do to help your child continue to recover at home.

Development of templates. We engaged families throughout the process of creating general and disease-specific discharge templates. After a specific template was created and reviewed by the parents on our team, it was sent to members of the institutional Patient Education Committee, which includes parents and local health literacy experts, to review and critique. Feedback from the reviewers was incorporated into the templates prior to use in the EHR.

Postdischarge phone calls.A convenience sample of families discharged from the satellite campus was called 24 to 48 hours after discharge over a 2-week period in January, 2016. A member of our improvement team solicited feedback from families about the quality of the discharge instructions. Families were asked if discharge instructions were reviewed with them prior to going home, if they were given a copy of the instructions, how they would rate the ability to read and use the information, and if there were additional pieces of information that would have improved the instructions.

Standardization of Instructions

Education. A presentation was created and shared with medical providers; it was re-disseminated monthly to new residents rotating onto the service and to the attendings, fellows, and NPs scheduled for shifts during the month. This education continued for the duration of the study. The presentation included the definition of health literacy, scope of the problem, examples of poorly written discharge instructions, and tips on how to write readable and understandable instructions. Laminated cards that included tips on how to write instructions were also placed on work stations.

While the general template was an important first step, the content relied heavily on free text by providers, which could still lead to instructions written at a high reading level. Thus, disease-specific discharge instruction templates were created with prepopulated information that was written at a reading level at or below 7^th grade level (Figure 2). The diseases were prioritized based on the most common diagnoses on our HM service. Each template included information under each of the subheadings noted in the general template. Twelve disease-specific templates were tested and ultimately embedded in the EHR; the general template remained for use when the discharge diagnosis was not covered by a disease-specific template.

Medical Staff Engagement

Previously described tests of change also aimed to enhance staff engagement. These included frequent e-mails, discussion of the QI efforts at specific team meetings, and the creation of visual cues posted at computer work stations, which prompted staff to begin to work on discharge instructions soon after admission.

Audit and Feedback of Data

Weekly phone calls. One team updated clinicians through a regularly scheduled bi-weekly phone conference. The phone conference was established prior to our work and was designed to relay pertinent information to attendings and NPs who work at the satellite hospital. During the phone conferences, clinicians were notified of current performance on discharge instruction readability and specific tests of change for the week. Additionally, providers gave feedback about the improvement efforts. These updates continued for the first 6 months of the project until sustained improvements were observed.

E-mails. Weekly e-mails were sent to all providers scheduled for clinical time at the satellite campus. The e-mail contained information on current tests of change, a list of discharge instruction templates that were available in the EHR, and the annotated run chart illustrating readability levels over time.

Additionally, individual e-mails were sent to each provider after review of the written discharge instructions for the week. Providers were given information on the number of discharge instructions they personally composed, the percentage of those instructions that were written at or below 7^th grade level, and specific feedback on how their written instructions could be improved. We also encouraged feedback from each provider to better identify barriers to achieving our goal.

Study of the Interventions

Baseline data included a review of all instructions for patients discharged from the satellite campus from the end of April 2015 through mid-September 2015. The time period for testing of interventions during the fall and winter months allowed for rapid cycle learning due to higher patient census and predictability of admissions for specific diagnosis (ie, asthma and bronchiolitis). An automated report was generated from the EHR weekly with specific demographics and identifiers for patient discharged over the past 7 days, including patient age, gender, length of stay, discharge diagnosis, and insurance classification. Data was collected during the intervention period via structured review of the discharge instructions in the EHR by the principal investigator or a trained research coordinator. Discharge instructions for medically cleared mental health patients admitted to hospital medicine while awaiting psychiatric bed availability and patients and parents who were non-English speaking were excluded from review. All other instructions for patients discharged from the HM service at our Liberty Campus were included for review.

Measures

Readability, our primary measure of interest, was calculated using the mean score from the following formulas: Flesch Kincaid Grade Level,²³ Simple Measure of Gobbledygook Index,²⁴ Coleman-Liau Index,²⁵ Gunning-Fog Index,²⁶ and Automated Readability Index²⁷ by means of an online platform (https://readability-score.com).²⁸ This platform was chosen because it incorporated a variety of formulas, was user-friendly, and required minimal data cleaning. Each of the readability formulas have been used to assesses readability of health information given to patients and families.^29,30 The threshold of 7th grade is in alignment with our institutional policy for educational materials and with recommendations from several government agencies.^5,12

Analysis

A statistical process control p-chart was used to analyze our primary measure of readability, dichotomized as percent discharge instructions written at or below 7th grade level. Run charts were used to follow mean reading level of discharge instructions and our process measure of percent of discharge instruction written with a general or disease-specific standardized template. Run chart and control chart rules for identifying special cause were used for midline shifts.³¹

The Table includes the demographic and clinical information of patients included in our analyses. Through sequential interventions, the percentage of discharge instructions written at or below 7th grade readability level increased from a mean of 13% to more than 80% in 3 months (Figure 3). Furthermore, the mean was sustained above 90% for 10 months and at 98% for the last 4 months. The use of 1 of the 13 EHR templates increased from 0% to 96% and was associated with the largest impact on the overall improvements (Supplemental Figure 1). Additionally, the average reading level of the discharge instructions decreased from 10th grade to 6th grade level (Supplemental Figure 2).

Qualitative comments from providers about the discharge instructions included:

“Are these [discharge instructions] available at base??  Great resource for interns.”
“These [discharge] instructions make the [discharge] process so easy!!! Love these...”
“Also feel like they have helped my discharge teaching in the room!”

Qualitative comments from families postdischarge included:
“I thought the instructions were very clear and easy to read. I especially thought that highlighting the important areas really helped.”
“I think this form looks great, and I really like the idea of having your child’s name on it.”

Through sequential Plan-Do Study-Act cycles, we increased the percentage of discharge instructions written at or below 7^th grade reading level from 13% to 98%. Our most impactful intervention was the creation and dissemination of standardized disease-specific discharge instruction templates. Our findings complement evidence in the adult and pediatric literature that the use of standardized, disease-specific discharge instruction templates may improve readability of instructions.^32,33 And, while quality improvement efforts have been employed to improve the discharge process for patients,^34-36 this is the first study in the inpatient setting that, to our knowledge, specifically addresses discharge instructions using quality improvement methods.

Our work targeted the critical intersection between individual health literacy, an individual’s capacity to acquire, interpret, and use health information, and the necessary changes needed within our healthcare system to ensure that appropriately written instructions are given to patients and families.^17,37 Our efforts focused on improving discharge instructions answer the call to consider health literacy a modifiable clinical risk factor.³⁷ Furthermore, we address the 6 aims for quality healthcare delivery: 1) safe, timely, efficient and equitable delivery of care through the creation and dissemination of standardized instructions that are written at the appropriate reading level for families to ease hospital-to-home transitions and streamline the workflow of medical providers; 2) effective education of medical providers on health literacy concepts; and 3) family-centeredness through the involvement of families in our QI efforts. While previous QI efforts to improve hospital-to-home transitions have focused on medication reconciliation, communication with primary care physicians, follow-up appointments, and timely discharges of patients, none have specifically focused on the quality of discharge instructions.^34-36

Most physicians do not receive education about how to write information that is readable and understandable; more than half of providers desired more education in this area.³⁸ Furthermore, pediatric providers may overestimate parental health literacy levels,³⁹ which may contribute to variability in the readability of written health materials. While education alone can contribute to a provider’s ability to create readable instructions, we note the improvement after the introduction of disease templates to demonstrate the importance of workflow-integrated higher reliability interventions to sustain improvements.

Our baseline poor readability rates were due to limited knowledge by frontline providers composing the instructions and a system in which an important element for successful hospital-to-home transitions was not tackled until patients were ready for discharge. Streamlining of the discharge process, including the creation of discharge instructions, may lead to improved efficiency, fewer discrepancies, more effective communication, and an enhanced family experience. Moreover, the success of our improvement work was due to key stakeholders, including parents, being a part of the team and the notable buy-in from providers.

Our work was not without limitations. We excluded non-English speaking families from the study. We were unable to measure reading level of our population directly and instead based our goals on national estimates. Our primary measure was readability, which is only 1 piece contributing to quality discharge instructions. Understandability and actionability are also important considerations; ^17,20,29,40 however, improvements in these areas were limited by our design options within the EHR. Our efforts focused on children with common general pediatric diagnoses, and it is unclear how our interventions would generalize to medically complex patients with more volume of information to communicate at discharge and with uncommon diagnoses that are less readily incorporated into standardized templates. Relatedly, our work occurred at the satellite campus of our tertiary care center and may not represent generalizable material or methods to implement templates at our main campus location or at other hospitals. To begin to better understand this, we have spread to HM patients at our main campus, including medically complex patients with technology dependence and/or neurological impairments. Standardized, disease-specific templates most relevant to this population as well as several patient specific templates, for those with frequent readmissions due to medical complexity, have been created and are actively being tested.

In conclusion, in using interventions targeted at standardization of discharge instructions and timely feedback to staff, we saw rapid, dramatic, and sustained improvement in the readability of discharge instructions. Next steps include adaptation and spread to other patient populations and care teams, collaborations with other centers, and assessing the impact of effectively written discharge instructions on patient outcomes, such as adverse drug events, readmission rates, and family experience.

Disclosure

No external funding was secured for this study. Dr. Brady is supported by a Patient-Centered Outcomes Research Mentored Clinical Investigator Award from the Agency for Healthcare Research and Quality, Award Number K08HS023827. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding organizations. The funding organization had no role in the design, preparation, review, or approval of this paper; nor the decision to submit the manuscript for publication. The authors have no financial relationships relevant to this article to disclose.

The transition from hospital to home can be overwhelming for caregivers.¹ Stress of hospitalization coupled with the expectation of families to execute postdischarge care plans make understandable discharge communication critical. Communication failures, inadequate education, absence of caregiver confidence, and lack of clarity regarding care plans may prohibit smooth transitions and lead to adverse postdischarge outcomes.^2-4

Health literacy plays a pivotal role in caregivers’ capacity to navigate the healthcare system, comprehend, and execute care plans. An estimated 90 million Americans have limited health literacy that may negatively impact the provision of safe and quality care^5,6 and be a risk factor for poor outcomes, including increased emergency department (ED) utilization and readmission rates.^7-9 Readability strongly influences the effectiveness of written materials.¹⁰ However, written medical information for patients and families are frequently between the 10^th and 12^th grade reading levels; more than 75% of all pediatric health information is written at or above 10^th grade reading level.¹¹ Government agencies recommend between a 6^th and 8^th grade reading level, for written material;^5,12,13 written discharge instructions have been identified as an important quality metric for hospital-to-home transitions.^14-16

At our center, we found that discharge instructions were commonly written at high reading levels and often incomplete.¹⁷ Poor discharge instructions may contribute to increased readmission rates and unnecessary ED visits.^9,18 Our global aim targeted improved health-literate written information, including understandability and completeness.

Our specific aim was to increase the percentage of discharge instructions written at or below the 7th grade level for hospital medicine (HM) patients on a community hospital pediatric unit from 13% to 80% in 6 months.

Context

The improvement work took place at a 42-bed inpatient pediatric unit at a community satellite of our large, urban, academic hospital. The unit is staffed by medical providers including attendings, fellows, nurse practitioners (NPs), and senior pediatric residents, and had more than 1000 HM discharges in fiscal year 2016. Children with common general pediatric diagnoses are admitted to this service; postsurgical patients are not admitted primarily to the HM service. In Cincinnati, the neighborhood-level high school drop-out rates are as high as 64%.¹⁹ Discharge instructions are written by medical providers in the electronic health record (EHR). A printed copy is given to families and verbally reviewed by a bedside nurse prior to discharge. Quality improvement (QI) efforts focused on discharge instructions were ignited by a prior review of 200 discharge instructions that showed they were difficult to read (median reading level of 10^th grade), poorly understandable (36% of instructions met the threshold of understandability as measured by the Patient Education Materials Assessment Tool²⁰) and were missing key elements of information.¹⁷

Improvement Team

The improvement team consisted of 4 pediatric hospitalists, 2 NPs, 1 nurse educator with health literacy expertise, 1 pediatric resident, 1 fourth-year medical student, 1 QI consultant, and 2 parents who had first-hand experience on the HM service. The improvement team observed the discharge process, including roles of the provider, nurse and family, outlined a process map, and created a modified failure mode and effect analysis.²¹ Prior to our work, discharge instructions written by providers often occurred as a last step, and the content was created as free text or from nonstandardized templates. Key drivers that informed interventions were determined and revised over time (Figure 1). The study was reviewed by our institutional review board and deemed not human subjects research.

Improvement Activities

Key drivers were identified, and interventions were executed using Plan-Do Study-Act cycles.²² The key drivers thought to be critical for the success of the QI efforts were family engagement; standardization of discharge instructions; medical staff engagement; and audit and feedback of data. The corresponding interventions were as follows:

Family Engagement

Understanding the discharge information families desired. Prior to testing, 10 families admitted to the HM service were asked about the discharge experience. We asked families about information they wanted in written discharge instructions: 1) reasons to call your primary doctor or return to the hospital; 2) when to see your primary doctor for a follow-up visit; 3) the phone number to reach your child’s doctor; 4) more information about why your child was admitted; 5) information about new medications; and 6) what to do to help your child continue to recover at home.

Development of templates. We engaged families throughout the process of creating general and disease-specific discharge templates. After a specific template was created and reviewed by the parents on our team, it was sent to members of the institutional Patient Education Committee, which includes parents and local health literacy experts, to review and critique. Feedback from the reviewers was incorporated into the templates prior to use in the EHR.

Postdischarge phone calls.A convenience sample of families discharged from the satellite campus was called 24 to 48 hours after discharge over a 2-week period in January, 2016. A member of our improvement team solicited feedback from families about the quality of the discharge instructions. Families were asked if discharge instructions were reviewed with them prior to going home, if they were given a copy of the instructions, how they would rate the ability to read and use the information, and if there were additional pieces of information that would have improved the instructions.

Standardization of Instructions

Education. A presentation was created and shared with medical providers; it was re-disseminated monthly to new residents rotating onto the service and to the attendings, fellows, and NPs scheduled for shifts during the month. This education continued for the duration of the study. The presentation included the definition of health literacy, scope of the problem, examples of poorly written discharge instructions, and tips on how to write readable and understandable instructions. Laminated cards that included tips on how to write instructions were also placed on work stations.

While the general template was an important first step, the content relied heavily on free text by providers, which could still lead to instructions written at a high reading level. Thus, disease-specific discharge instruction templates were created with prepopulated information that was written at a reading level at or below 7^th grade level (Figure 2). The diseases were prioritized based on the most common diagnoses on our HM service. Each template included information under each of the subheadings noted in the general template. Twelve disease-specific templates were tested and ultimately embedded in the EHR; the general template remained for use when the discharge diagnosis was not covered by a disease-specific template.

Medical Staff Engagement

Previously described tests of change also aimed to enhance staff engagement. These included frequent e-mails, discussion of the QI efforts at specific team meetings, and the creation of visual cues posted at computer work stations, which prompted staff to begin to work on discharge instructions soon after admission.

Audit and Feedback of Data

Weekly phone calls. One team updated clinicians through a regularly scheduled bi-weekly phone conference. The phone conference was established prior to our work and was designed to relay pertinent information to attendings and NPs who work at the satellite hospital. During the phone conferences, clinicians were notified of current performance on discharge instruction readability and specific tests of change for the week. Additionally, providers gave feedback about the improvement efforts. These updates continued for the first 6 months of the project until sustained improvements were observed.

E-mails. Weekly e-mails were sent to all providers scheduled for clinical time at the satellite campus. The e-mail contained information on current tests of change, a list of discharge instruction templates that were available in the EHR, and the annotated run chart illustrating readability levels over time.

Additionally, individual e-mails were sent to each provider after review of the written discharge instructions for the week. Providers were given information on the number of discharge instructions they personally composed, the percentage of those instructions that were written at or below 7^th grade level, and specific feedback on how their written instructions could be improved. We also encouraged feedback from each provider to better identify barriers to achieving our goal.

Study of the Interventions

Baseline data included a review of all instructions for patients discharged from the satellite campus from the end of April 2015 through mid-September 2015. The time period for testing of interventions during the fall and winter months allowed for rapid cycle learning due to higher patient census and predictability of admissions for specific diagnosis (ie, asthma and bronchiolitis). An automated report was generated from the EHR weekly with specific demographics and identifiers for patient discharged over the past 7 days, including patient age, gender, length of stay, discharge diagnosis, and insurance classification. Data was collected during the intervention period via structured review of the discharge instructions in the EHR by the principal investigator or a trained research coordinator. Discharge instructions for medically cleared mental health patients admitted to hospital medicine while awaiting psychiatric bed availability and patients and parents who were non-English speaking were excluded from review. All other instructions for patients discharged from the HM service at our Liberty Campus were included for review.

Measures

Readability, our primary measure of interest, was calculated using the mean score from the following formulas: Flesch Kincaid Grade Level,²³ Simple Measure of Gobbledygook Index,²⁴ Coleman-Liau Index,²⁵ Gunning-Fog Index,²⁶ and Automated Readability Index²⁷ by means of an online platform (https://readability-score.com).²⁸ This platform was chosen because it incorporated a variety of formulas, was user-friendly, and required minimal data cleaning. Each of the readability formulas have been used to assesses readability of health information given to patients and families.^29,30 The threshold of 7th grade is in alignment with our institutional policy for educational materials and with recommendations from several government agencies.^5,12

Analysis

A statistical process control p-chart was used to analyze our primary measure of readability, dichotomized as percent discharge instructions written at or below 7th grade level. Run charts were used to follow mean reading level of discharge instructions and our process measure of percent of discharge instruction written with a general or disease-specific standardized template. Run chart and control chart rules for identifying special cause were used for midline shifts.³¹

The Table includes the demographic and clinical information of patients included in our analyses. Through sequential interventions, the percentage of discharge instructions written at or below 7th grade readability level increased from a mean of 13% to more than 80% in 3 months (Figure 3). Furthermore, the mean was sustained above 90% for 10 months and at 98% for the last 4 months. The use of 1 of the 13 EHR templates increased from 0% to 96% and was associated with the largest impact on the overall improvements (Supplemental Figure 1). Additionally, the average reading level of the discharge instructions decreased from 10th grade to 6th grade level (Supplemental Figure 2).

Qualitative comments from providers about the discharge instructions included:

“Are these [discharge instructions] available at base??  Great resource for interns.”
“These [discharge] instructions make the [discharge] process so easy!!! Love these...”
“Also feel like they have helped my discharge teaching in the room!”

Qualitative comments from families postdischarge included:
“I thought the instructions were very clear and easy to read. I especially thought that highlighting the important areas really helped.”
“I think this form looks great, and I really like the idea of having your child’s name on it.”

Through sequential Plan-Do Study-Act cycles, we increased the percentage of discharge instructions written at or below 7^th grade reading level from 13% to 98%. Our most impactful intervention was the creation and dissemination of standardized disease-specific discharge instruction templates. Our findings complement evidence in the adult and pediatric literature that the use of standardized, disease-specific discharge instruction templates may improve readability of instructions.^32,33 And, while quality improvement efforts have been employed to improve the discharge process for patients,^34-36 this is the first study in the inpatient setting that, to our knowledge, specifically addresses discharge instructions using quality improvement methods.

Our work targeted the critical intersection between individual health literacy, an individual’s capacity to acquire, interpret, and use health information, and the necessary changes needed within our healthcare system to ensure that appropriately written instructions are given to patients and families.^17,37 Our efforts focused on improving discharge instructions answer the call to consider health literacy a modifiable clinical risk factor.³⁷ Furthermore, we address the 6 aims for quality healthcare delivery: 1) safe, timely, efficient and equitable delivery of care through the creation and dissemination of standardized instructions that are written at the appropriate reading level for families to ease hospital-to-home transitions and streamline the workflow of medical providers; 2) effective education of medical providers on health literacy concepts; and 3) family-centeredness through the involvement of families in our QI efforts. While previous QI efforts to improve hospital-to-home transitions have focused on medication reconciliation, communication with primary care physicians, follow-up appointments, and timely discharges of patients, none have specifically focused on the quality of discharge instructions.^34-36

Most physicians do not receive education about how to write information that is readable and understandable; more than half of providers desired more education in this area.³⁸ Furthermore, pediatric providers may overestimate parental health literacy levels,³⁹ which may contribute to variability in the readability of written health materials. While education alone can contribute to a provider’s ability to create readable instructions, we note the improvement after the introduction of disease templates to demonstrate the importance of workflow-integrated higher reliability interventions to sustain improvements.

Our baseline poor readability rates were due to limited knowledge by frontline providers composing the instructions and a system in which an important element for successful hospital-to-home transitions was not tackled until patients were ready for discharge. Streamlining of the discharge process, including the creation of discharge instructions, may lead to improved efficiency, fewer discrepancies, more effective communication, and an enhanced family experience. Moreover, the success of our improvement work was due to key stakeholders, including parents, being a part of the team and the notable buy-in from providers.

Our work was not without limitations. We excluded non-English speaking families from the study. We were unable to measure reading level of our population directly and instead based our goals on national estimates. Our primary measure was readability, which is only 1 piece contributing to quality discharge instructions. Understandability and actionability are also important considerations; ^17,20,29,40 however, improvements in these areas were limited by our design options within the EHR. Our efforts focused on children with common general pediatric diagnoses, and it is unclear how our interventions would generalize to medically complex patients with more volume of information to communicate at discharge and with uncommon diagnoses that are less readily incorporated into standardized templates. Relatedly, our work occurred at the satellite campus of our tertiary care center and may not represent generalizable material or methods to implement templates at our main campus location or at other hospitals. To begin to better understand this, we have spread to HM patients at our main campus, including medically complex patients with technology dependence and/or neurological impairments. Standardized, disease-specific templates most relevant to this population as well as several patient specific templates, for those with frequent readmissions due to medical complexity, have been created and are actively being tested.

In conclusion, in using interventions targeted at standardization of discharge instructions and timely feedback to staff, we saw rapid, dramatic, and sustained improvement in the readability of discharge instructions. Next steps include adaptation and spread to other patient populations and care teams, collaborations with other centers, and assessing the impact of effectively written discharge instructions on patient outcomes, such as adverse drug events, readmission rates, and family experience.

Disclosure

No external funding was secured for this study. Dr. Brady is supported by a Patient-Centered Outcomes Research Mentored Clinical Investigator Award from the Agency for Healthcare Research and Quality, Award Number K08HS023827. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding organizations. The funding organization had no role in the design, preparation, review, or approval of this paper; nor the decision to submit the manuscript for publication. The authors have no financial relationships relevant to this article to disclose.

The transition from hospital to home can be overwhelming for caregivers.¹ Stress of hospitalization coupled with the expectation of families to execute postdischarge care plans make understandable discharge communication critical. Communication failures, inadequate education, absence of caregiver confidence, and lack of clarity regarding care plans may prohibit smooth transitions and lead to adverse postdischarge outcomes.^2-4

Health literacy plays a pivotal role in caregivers’ capacity to navigate the healthcare system, comprehend, and execute care plans. An estimated 90 million Americans have limited health literacy that may negatively impact the provision of safe and quality care^5,6 and be a risk factor for poor outcomes, including increased emergency department (ED) utilization and readmission rates.^7-9 Readability strongly influences the effectiveness of written materials.¹⁰ However, written medical information for patients and families are frequently between the 10^th and 12^th grade reading levels; more than 75% of all pediatric health information is written at or above 10^th grade reading level.¹¹ Government agencies recommend between a 6^th and 8^th grade reading level, for written material;^5,12,13 written discharge instructions have been identified as an important quality metric for hospital-to-home transitions.^14-16

At our center, we found that discharge instructions were commonly written at high reading levels and often incomplete.¹⁷ Poor discharge instructions may contribute to increased readmission rates and unnecessary ED visits.^9,18 Our global aim targeted improved health-literate written information, including understandability and completeness.

Our specific aim was to increase the percentage of discharge instructions written at or below the 7th grade level for hospital medicine (HM) patients on a community hospital pediatric unit from 13% to 80% in 6 months.

Context

The improvement work took place at a 42-bed inpatient pediatric unit at a community satellite of our large, urban, academic hospital. The unit is staffed by medical providers including attendings, fellows, nurse practitioners (NPs), and senior pediatric residents, and had more than 1000 HM discharges in fiscal year 2016. Children with common general pediatric diagnoses are admitted to this service; postsurgical patients are not admitted primarily to the HM service. In Cincinnati, the neighborhood-level high school drop-out rates are as high as 64%.¹⁹ Discharge instructions are written by medical providers in the electronic health record (EHR). A printed copy is given to families and verbally reviewed by a bedside nurse prior to discharge. Quality improvement (QI) efforts focused on discharge instructions were ignited by a prior review of 200 discharge instructions that showed they were difficult to read (median reading level of 10^th grade), poorly understandable (36% of instructions met the threshold of understandability as measured by the Patient Education Materials Assessment Tool²⁰) and were missing key elements of information.¹⁷

Improvement Team

The improvement team consisted of 4 pediatric hospitalists, 2 NPs, 1 nurse educator with health literacy expertise, 1 pediatric resident, 1 fourth-year medical student, 1 QI consultant, and 2 parents who had first-hand experience on the HM service. The improvement team observed the discharge process, including roles of the provider, nurse and family, outlined a process map, and created a modified failure mode and effect analysis.²¹ Prior to our work, discharge instructions written by providers often occurred as a last step, and the content was created as free text or from nonstandardized templates. Key drivers that informed interventions were determined and revised over time (Figure 1). The study was reviewed by our institutional review board and deemed not human subjects research.

Improvement Activities

Key drivers were identified, and interventions were executed using Plan-Do Study-Act cycles.²² The key drivers thought to be critical for the success of the QI efforts were family engagement; standardization of discharge instructions; medical staff engagement; and audit and feedback of data. The corresponding interventions were as follows:

Family Engagement

Understanding the discharge information families desired. Prior to testing, 10 families admitted to the HM service were asked about the discharge experience. We asked families about information they wanted in written discharge instructions: 1) reasons to call your primary doctor or return to the hospital; 2) when to see your primary doctor for a follow-up visit; 3) the phone number to reach your child’s doctor; 4) more information about why your child was admitted; 5) information about new medications; and 6) what to do to help your child continue to recover at home.

Development of templates. We engaged families throughout the process of creating general and disease-specific discharge templates. After a specific template was created and reviewed by the parents on our team, it was sent to members of the institutional Patient Education Committee, which includes parents and local health literacy experts, to review and critique. Feedback from the reviewers was incorporated into the templates prior to use in the EHR.

Postdischarge phone calls.A convenience sample of families discharged from the satellite campus was called 24 to 48 hours after discharge over a 2-week period in January, 2016. A member of our improvement team solicited feedback from families about the quality of the discharge instructions. Families were asked if discharge instructions were reviewed with them prior to going home, if they were given a copy of the instructions, how they would rate the ability to read and use the information, and if there were additional pieces of information that would have improved the instructions.

Standardization of Instructions

Education. A presentation was created and shared with medical providers; it was re-disseminated monthly to new residents rotating onto the service and to the attendings, fellows, and NPs scheduled for shifts during the month. This education continued for the duration of the study. The presentation included the definition of health literacy, scope of the problem, examples of poorly written discharge instructions, and tips on how to write readable and understandable instructions. Laminated cards that included tips on how to write instructions were also placed on work stations.

While the general template was an important first step, the content relied heavily on free text by providers, which could still lead to instructions written at a high reading level. Thus, disease-specific discharge instruction templates were created with prepopulated information that was written at a reading level at or below 7^th grade level (Figure 2). The diseases were prioritized based on the most common diagnoses on our HM service. Each template included information under each of the subheadings noted in the general template. Twelve disease-specific templates were tested and ultimately embedded in the EHR; the general template remained for use when the discharge diagnosis was not covered by a disease-specific template.

Medical Staff Engagement

Previously described tests of change also aimed to enhance staff engagement. These included frequent e-mails, discussion of the QI efforts at specific team meetings, and the creation of visual cues posted at computer work stations, which prompted staff to begin to work on discharge instructions soon after admission.

Audit and Feedback of Data

Weekly phone calls. One team updated clinicians through a regularly scheduled bi-weekly phone conference. The phone conference was established prior to our work and was designed to relay pertinent information to attendings and NPs who work at the satellite hospital. During the phone conferences, clinicians were notified of current performance on discharge instruction readability and specific tests of change for the week. Additionally, providers gave feedback about the improvement efforts. These updates continued for the first 6 months of the project until sustained improvements were observed.

E-mails. Weekly e-mails were sent to all providers scheduled for clinical time at the satellite campus. The e-mail contained information on current tests of change, a list of discharge instruction templates that were available in the EHR, and the annotated run chart illustrating readability levels over time.

Additionally, individual e-mails were sent to each provider after review of the written discharge instructions for the week. Providers were given information on the number of discharge instructions they personally composed, the percentage of those instructions that were written at or below 7^th grade level, and specific feedback on how their written instructions could be improved. We also encouraged feedback from each provider to better identify barriers to achieving our goal.

Study of the Interventions

Baseline data included a review of all instructions for patients discharged from the satellite campus from the end of April 2015 through mid-September 2015. The time period for testing of interventions during the fall and winter months allowed for rapid cycle learning due to higher patient census and predictability of admissions for specific diagnosis (ie, asthma and bronchiolitis). An automated report was generated from the EHR weekly with specific demographics and identifiers for patient discharged over the past 7 days, including patient age, gender, length of stay, discharge diagnosis, and insurance classification. Data was collected during the intervention period via structured review of the discharge instructions in the EHR by the principal investigator or a trained research coordinator. Discharge instructions for medically cleared mental health patients admitted to hospital medicine while awaiting psychiatric bed availability and patients and parents who were non-English speaking were excluded from review. All other instructions for patients discharged from the HM service at our Liberty Campus were included for review.

Measures

Readability, our primary measure of interest, was calculated using the mean score from the following formulas: Flesch Kincaid Grade Level,²³ Simple Measure of Gobbledygook Index,²⁴ Coleman-Liau Index,²⁵ Gunning-Fog Index,²⁶ and Automated Readability Index²⁷ by means of an online platform (https://readability-score.com).²⁸ This platform was chosen because it incorporated a variety of formulas, was user-friendly, and required minimal data cleaning. Each of the readability formulas have been used to assesses readability of health information given to patients and families.^29,30 The threshold of 7th grade is in alignment with our institutional policy for educational materials and with recommendations from several government agencies.^5,12

Analysis

A statistical process control p-chart was used to analyze our primary measure of readability, dichotomized as percent discharge instructions written at or below 7th grade level. Run charts were used to follow mean reading level of discharge instructions and our process measure of percent of discharge instruction written with a general or disease-specific standardized template. Run chart and control chart rules for identifying special cause were used for midline shifts.³¹

The Table includes the demographic and clinical information of patients included in our analyses. Through sequential interventions, the percentage of discharge instructions written at or below 7th grade readability level increased from a mean of 13% to more than 80% in 3 months (Figure 3). Furthermore, the mean was sustained above 90% for 10 months and at 98% for the last 4 months. The use of 1 of the 13 EHR templates increased from 0% to 96% and was associated with the largest impact on the overall improvements (Supplemental Figure 1). Additionally, the average reading level of the discharge instructions decreased from 10th grade to 6th grade level (Supplemental Figure 2).

Qualitative comments from providers about the discharge instructions included:

“Are these [discharge instructions] available at base??  Great resource for interns.”
“These [discharge] instructions make the [discharge] process so easy!!! Love these...”
“Also feel like they have helped my discharge teaching in the room!”

Qualitative comments from families postdischarge included:
“I thought the instructions were very clear and easy to read. I especially thought that highlighting the important areas really helped.”
“I think this form looks great, and I really like the idea of having your child’s name on it.”

Through sequential Plan-Do Study-Act cycles, we increased the percentage of discharge instructions written at or below 7^th grade reading level from 13% to 98%. Our most impactful intervention was the creation and dissemination of standardized disease-specific discharge instruction templates. Our findings complement evidence in the adult and pediatric literature that the use of standardized, disease-specific discharge instruction templates may improve readability of instructions.^32,33 And, while quality improvement efforts have been employed to improve the discharge process for patients,^34-36 this is the first study in the inpatient setting that, to our knowledge, specifically addresses discharge instructions using quality improvement methods.

Our work targeted the critical intersection between individual health literacy, an individual’s capacity to acquire, interpret, and use health information, and the necessary changes needed within our healthcare system to ensure that appropriately written instructions are given to patients and families.^17,37 Our efforts focused on improving discharge instructions answer the call to consider health literacy a modifiable clinical risk factor.³⁷ Furthermore, we address the 6 aims for quality healthcare delivery: 1) safe, timely, efficient and equitable delivery of care through the creation and dissemination of standardized instructions that are written at the appropriate reading level for families to ease hospital-to-home transitions and streamline the workflow of medical providers; 2) effective education of medical providers on health literacy concepts; and 3) family-centeredness through the involvement of families in our QI efforts. While previous QI efforts to improve hospital-to-home transitions have focused on medication reconciliation, communication with primary care physicians, follow-up appointments, and timely discharges of patients, none have specifically focused on the quality of discharge instructions.^34-36

Most physicians do not receive education about how to write information that is readable and understandable; more than half of providers desired more education in this area.³⁸ Furthermore, pediatric providers may overestimate parental health literacy levels,³⁹ which may contribute to variability in the readability of written health materials. While education alone can contribute to a provider’s ability to create readable instructions, we note the improvement after the introduction of disease templates to demonstrate the importance of workflow-integrated higher reliability interventions to sustain improvements.

Our baseline poor readability rates were due to limited knowledge by frontline providers composing the instructions and a system in which an important element for successful hospital-to-home transitions was not tackled until patients were ready for discharge. Streamlining of the discharge process, including the creation of discharge instructions, may lead to improved efficiency, fewer discrepancies, more effective communication, and an enhanced family experience. Moreover, the success of our improvement work was due to key stakeholders, including parents, being a part of the team and the notable buy-in from providers.

Our work was not without limitations. We excluded non-English speaking families from the study. We were unable to measure reading level of our population directly and instead based our goals on national estimates. Our primary measure was readability, which is only 1 piece contributing to quality discharge instructions. Understandability and actionability are also important considerations; ^17,20,29,40 however, improvements in these areas were limited by our design options within the EHR. Our efforts focused on children with common general pediatric diagnoses, and it is unclear how our interventions would generalize to medically complex patients with more volume of information to communicate at discharge and with uncommon diagnoses that are less readily incorporated into standardized templates. Relatedly, our work occurred at the satellite campus of our tertiary care center and may not represent generalizable material or methods to implement templates at our main campus location or at other hospitals. To begin to better understand this, we have spread to HM patients at our main campus, including medically complex patients with technology dependence and/or neurological impairments. Standardized, disease-specific templates most relevant to this population as well as several patient specific templates, for those with frequent readmissions due to medical complexity, have been created and are actively being tested.

In conclusion, in using interventions targeted at standardization of discharge instructions and timely feedback to staff, we saw rapid, dramatic, and sustained improvement in the readability of discharge instructions. Next steps include adaptation and spread to other patient populations and care teams, collaborations with other centers, and assessing the impact of effectively written discharge instructions on patient outcomes, such as adverse drug events, readmission rates, and family experience.

Disclosure

No external funding was secured for this study. Dr. Brady is supported by a Patient-Centered Outcomes Research Mentored Clinical Investigator Award from the Agency for Healthcare Research and Quality, Award Number K08HS023827. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding organizations. The funding organization had no role in the design, preparation, review, or approval of this paper; nor the decision to submit the manuscript for publication. The authors have no financial relationships relevant to this article to disclose.