A. Scott Keller, MD, MS

A 40‐year‐old Sudanese man was admitted due to worsening abdominal pain with recurrent ascites. He had a history of hepatitis B (HBV) infection and diabetes. He previously drank 3 beers per day on the weekends, but he had not consumed alcohol in over a year. He was born in Sudan but lived in Egypt most of his adult life; he immigrated to the United States 6 years previously. He was hospitalized out of state 9 months ago for a swollen abdomen and underwent an exploratory laparotomy that reportedly was unremarkable except for ascites.

Portal hypertension due to liver disease is the most common cause of ascites. This patient has a known risk factor for liver disease (history of HBV infection). Although his reported alcohol consumption is low, there is a synergistic effect on liver injury in the setting of chronic hepatitis. Abdominal pain in the setting of ascites needs to be urgently evaluated to exclude spontaneous bacterial peritonitis (SBP). Also, because chronic HBV infection is the major risk factor for hepatocellular carcinoma in the world, malignant ascites is in the differential. Hepatic vascular thrombosis and tuberculous peritonitis (given the patient's country of origin and travel history) also should be considered. The most appropriate initial test would be a diagnostic paracentesis to support or exclude the presence of SBP and direct the evaluation toward liver disease or other less‐common causes of ascites.

The patient was seen as an outpatient 5 months prior to admission with transient fever and joint pains. Laboratory studies at that visit were notable for a serum albumin of 3.2 g/dL (normal 3.55), 2.4 g of predicted 24‐hour protein on urinalysis (normal <30 mg per 24 hours), creatinine of 0.5 mg/dL (normal 0.81.3), and a positive hepatitis B surface antibody. The working diagnosis was a nonspecific viral syndrome and his symptoms resolved without treatment. One month later, he developed ascites and mild lower extremity edema. Additional laboratory studies at that time showed a normocytic anemia with hemoglobin 11.7 g/dL (normal 13.517.5) and leukopenia with white blood cell count of 2.4 10⁹/L (normal 3.510.5), neutrophil count of 1.45 10⁹/L (normal 1.77.0), and lymphocyte count of 0.58 10⁹/L (normal 0.902.90). Transaminases, serum bilirubin, prothrombin time, alpha fetoprotein, and peripheral blood smear were normal. Human immunodeficiency virus antibody screen and QuantiFERON‐TB assay were negative. Hemoglobin A1c was 6.2% (normal 4.06.0). Repeat urinalysis demonstrated 883 mg of predicted 24‐hour protein. Computed tomography (CT) of the abdomen showed a large amount of intra‐abdominal ascites; the liver and spleen were normal, and there were no varices or other evidence of portal hypertension. Echocardiogram was normal except for a small inferior vena cava (IVC) and a mildly increased right ventricular systolic pressure of 32 mm Hg (systolic blood pressure 98 mm Hg). Due to the indeterminate cause for the patient's ascites, referral was made for gastroenterology evaluation with consideration for a paracentesis.

Cirrhotic ascites seems less likely. Postsinusoidal causes of portal hypertension (eg, cardiomyopathy) are also less likely given the absence of suggestive findings on echocardiography. Malignant ascites also appears less probable in the absence of suggestive findings such as mass lesions, lymphadenopathy, or peritoneal carcinomatosis on CT imaging. The suspicion for tuberculous peritonitis is lower with the negative QuantiFERON‐TB test. Hypoalbuminemia, normocytic anemia, leukopenia, and proteinuria all suggest a systemic inflammatory condition (eg, systemic lupus erythematosus [SLE]) with inflammatory serositis causing ascites). Nephrotic syndrome can cause hypoalbuminemia, edema, and ascites, but his total urine protein losses of <3.5 grams per 24 hours are not in keeping with this diagnosis. Other uncommon causes of ascites such as chylous ascites have not yet been excluded. The most appropriate next step remains ascitic fluid analysis.

A paracentesis yielded 7.8 L of clear‐yellow fluid and improvement in his abdominal discomfort. Analysis showed 224 total nucleated cells/L with 2% neutrophils, 57% lymphocytes, and 37% monocytes. Ascites total protein was 3.8 g/dL and glucose was 55 mg/dL. Gram stain and culture were negative, and cytology was negative for malignancy but showed lymphocytes, plasma cells, monocytes, and reactive mesothelial cells interpreted as consistent with chronic inflammation. The serum‐ascites albumin gradient (SAAG) was not obtained.

With a low leukocyte count and a paucity of neutrophils, this is not SBP. The ascites fluid did not have a chylous appearance. The SAAG, which can distinguish between portal hypertensive and nonportal hypertensive causes for ascites using a cutoff of 1.1 g/dL, was not done. The total protein was high, arguing against cirrhosis. High protein ascites with a high SAAG would suggest a posthepatic source of portal hypertension (eg, Budd‐Chiari syndrome, constrictive pericarditis). High protein ascites with a low SAAG would suggest an inflammatory or malignant source of ascites. The relative lymphocytosis in the ascites fluid suggests an inflammatory process, but is a nonspecific finding. The negative cytology does not completely exclude a malignancy, but given the absence of findings on the CT, malignant ascites is less likely.

Three months before admission, the patient underwent a repeat large‐volume paracentesis and a liver biopsy. The biopsy showed ectopic portal vein branches consistent with hepatoportal sclerosis, but no actual sclerosis was identified. The pathologist concluded that the findings suggested noncirrhotic portal hypertension due to a vascular in‐flow abnormality. Abdominal ultrasound with Doppler was unremarkable other than slightly increased echogenicity of the liver. Magnetic resonance (MR) angiogram showed narrowing of the intra‐abdominal IVC at the level of the diaphragm. Because of concern that hepatic congestion from high pressures in the narrowed IVC was leading to poor vascular inflow as suggested by the biopsy findings, an inferior vena cavagram was performed. This study was normal, although no transhepatic pressure measurements were obtained. Three stool specimens and 2 urine specimens were negative for parasites. The patient required repeat large‐volume paracenteses monthly. SBP was again ruled out, but no other diagnostic labs were obtained. He had anorexia with poor oral intake each time his abdomen became distended.

The patient was started on furosemide 1 month prior to admission to the hospital but had only a slight improvement in the ascites. His other medications included insulin, tamsulosin, and hydrocodone‐acetaminophen. Five days prior to admission, he underwent a diagnostic laparoscopy, which showed only ascites and small adhesions to the anterior abdominal wall. There was no visual evidence of malignancy, and the surgeon commented that the liver was normal. No additional biopsies were obtained.

The liver biopsy findings could be seen in noncirrhotic portal hypertension, although this diagnosis would be unlikely without splenomegaly, varices, or other signs of portal hypertension. However, 2 possible etiologies for noncirrhotic portal hypertension in this patient would be hepatic congestion from the narrowed IVC (although the normal IVC study argues against this) and hepatic schistosomiasis. Schistosomiasis is an important cause of noncirrhotic portal hypertension in endemic areas like this patient's country of origin, but the negative stool and urine studies, combined with the lack of granulomas or fibrosis seen on biopsy, make this condition unlikely.

Systemic amyloidosis (primary or secondary) could also be a cause of ascites and could present with multiorgan involvement (diarrhea and nephrotic syndrome). Amyloid deposits would have probably been seen in the liver biopsy, if present, but may not have been apparent unless specific stains (Congo red) were performed.

Evaluation for systemic, inflammatory autoimmune processes is indicated. Serum autoantibodies (anti‐nuclear antibody [ANA] and extractable nuclear antigens), and a serum and 24‐hour urine protein electrophoresis would be appropriate diagnostic tests. Peritoneal biopsies would have been helpful to assess for serosal diseases.

The patient subsequently developed acute right‐sided abdominal pain requiring urgent evaluation and admission to the hospital. He was initially assessed by a general surgeon, who found no evidence of postoperative complications. His temperature was 36.7C, blood pressure 105/64, heart rate 82, respiratory rate 16, and oxygen saturation 97% on room air. He appeared chronically ill, but he was in no distress and he had a normal mental status. Cardiac exam was normal except for mild jugular venous distension. He had mild bibasilar lung crackles. His abdomen was distended with superficial abdominal tenderness and a fluid wave, but he had normal bowel sounds and no peritoneal signs. He had mild scrotal edema but no peripheral edema. Joint exam did not suggest synovitis and there were no rashes or oral ulcers. Lactate was 0.9 mmol/L (normal 0.62.3), albumin was 2.6 g/dL, and prealbumin was 9 mg/dL (normal 1938). Erythrocyte sedimentation rate and C‐reactive protein were 46 mm/hour (normal <22) and 33.1 mg/L (normal 8), respectively. He had a normocytic anemia and leukopenia. Liver tests and routine chemistries were normal. Serum protein electrophoresis indicated no monoclonal protein. Complete 24‐hour urine collection showed 1.2 g of protein (normal <102 mg). Paracentesis of 3.4 L demonstrated 227 total nucleated cells/L with 2% neutrophils. Following the fluid removal, he had improvement in his pain, which he felt was related to the ascites rather than the recent surgery. Ascites total protein was 3.9 g/dL and ascites albumin was 1.7 g/dL. Ascites culture was negative for infection. Serum Schistosoma immunoglobulin G (IgG) antibody was positive at 3.53 (normal <1.00).

Further history revealed prior episodes of polyarticular joint pain and swelling in his hands and knees 5 years before admission. At that time, he reported a diffuse, pruritic, papular body rash. In addition, he noticed that his fingertips and toes turned white with cold exposure.

Importantly, surgical and infectious complications have been excluded. High protein ascites with a low SAAG of 0.9 suggests an inflammatory source of ascites. The follow‐up clinical data (arthritis, normocytic anemia, leukopenia, rash, Raynaud's phenomenon) suggest a systemic inflammatory syndrome such as SLE, with accompanying serositis. Serologic testing for autoantibodies would be recommended. Peritoneal biopsies, if obtained, may have demonstrated chronic, inflammatory infiltrate (nonspecific) or leukocytoclastic vasculitis (strongly supportive).

ANA enzyme immunoassay was >12 U (normal 1.0 U). Extractable nuclear antigens revealed positive autoantibodies for anti‐SSA, anti‐SSB, and anti‐ribosomal P. Moreover, double‐stranded DNA IgG antibody was 120 IU/mL (normal <30 IU/mL) and C3, C4, and total complement levels were low.

The clinical data support a diagnosis of SLE with serositis. Treatment of the underlying connective tissue disease will typically result in resolution of the ascites; diuretic therapy is generally ineffective.

In consultation with rheumatology and gastroenterology specialists, the diagnosis of SLE was made based on criteria of serositis, persistent leukopenia, arthritis, renal disease (proteinuria), positive ANA, elevated ds‐DNA antibodies, and hypocomplementemia. MR imaging of the abdominal vasculature demonstrated no evidence of vasculitis. The patient was given intravenous methylprednisolone 1 g daily for 3 days followed by high‐dose oral corticosteroids with a gradual taper. He was also started on mycophenolate mofetil as a steroid‐sparing medication (which was later changed to leflunomide due to persistent leukopenia) and hydroxychloroquine. His isolated positive Schistosoma IgG antibody in the absence of other findings was consistent with past exposure or infection. The infectious disease specialist felt there was no evidence of active schistosomiasis, but recommended treatment with a single dose of praziquantel due to the potential benefit with low risk of side effects. The patient had ongoing improvement following dismissal. He had 1 additional paracentesis of 4.1 L, 10 days after his hospitalization, and his ascites and proteinuria resolved. At the 5‐year follow‐up visit, there had been no recurrence of abdominal ascites or abdominal pain. He remains on low‐dose prednisone at 5 mg daily, leflunomide, and hydroxychloroquine.

COMMENTARY

This patient had recurrent ascites with 29.6 L removed over the 4 months prior to admission and an additional 3.4 L during his hospitalization. His outpatient providers initially considered a portal hypertensive etiology of his ascites due to his history of HBV and prior alcohol use. They also appropriately investigated for a possible infectious process. They next directed their evaluation toward the liver biopsy findings, which raised concern for a vascular inflow abnormality. However, the evaluation could have been performed more rapidly and far more cost‐efficiently had a diagnostic paracentesis with calculation of the SAAG been performed early in the evaluation.

The SAAG, which was first described in 1983 by Par and colleagues, is a parameter reflecting the oncotic pressure gradient between the vascular bed and the interstitial splanchnic or ascitic fluid. [1] In the classic study by Runyon and colleagues, a SAAG difference of 1.1 g/dL correctly differentiated causes of ascites due to portal hypertension from those that were not due to portal hypertension 96.7% of the time. [2] Conditions such as nephrotic syndrome, peritoneal carcinomatosis, and serositis (lupus peritonitis) can cause ascites in patients without portal hypertension.

Serositis in the form of pleuritis and/or pericarditis is a common feature of SLE, and ascites has been described in 8% to 11% of SLE patients.[3] However, massive ascites due to lupus peritonitis as a presenting symptom is rare.[4] More common causes of ascites in the setting of SLE include nephrotic syndrome, heart failure, protein‐losing enteropathy, constrictive pericarditis, Budd‐Chiari syndrome, indolent infections such as tuberculosis, and chylous ascites.[5, 6, 7] Of note, lupus peritonitis may be chronic or acute. Chronic ascites develops insidiously with few manifestations of active lupus and may be painless, whereas ascites from acute lupus peritonitis typically develops rapidly and presents with acute abdominal pain and other signs of increased lupus activity.[3, 5, 6, 8, 9]

Ascites from lupus peritonitis may be due to marked serosal exudative accumulation with reduced absorptive capacity in the peritoneum.[3, 4, 10] Other possible causes include peritoneal inflammation from deposition of immune complexes or vasculitis of peritoneal vessels and visceral serous membranes.[4, 9, 11] Although subserosal and submucosal vasculitis have been found in acute ascites, chronic ascites may be related to scarring from vasculitis and serosal inflammation leading to poor venous and lymph drainage.[9] Ascitic fluid characteristics from lupus peritonitis include a SAAG <1.1, presence of white blood cells anywhere in a broad range from 10 to 1630/L, and a range of fluid protein from 3.4 to 4.7 mg/dL.[3] Although not tested in this patient, findings of low complement levels, positive ANA, and elevated anti‐DNA antibody in the ascitic fluid would be supportive of lupus peritonitis, but not specific.[5, 9, 12] Lupus erythematosus cells are occasionally found in the ascitic fluid, but do not rule out other causes of ascites.[9] On retrospective analysis, lupus erythematosus cells were not seen in this patient's pathology specimens.

Treatment of lupus peritonitis and ascites is with high‐dose glucocorticoid therapy, but many patients may need a second immunosuppressant, possibly because of impaired peritoneal circulation from chronic inflammation leading to decreased drug delivery.[13, 14] Chronic ascites may be recalcitrant to systemic glucocorticoids,[3] so a possible alternative therapy is intraperitoneal injection of triamcinolone, which successfully treated massive ascites in a patient who did not respond to oral glucocorticoid treatment.[13] Although ascites may be refractory in some patients, those with chronic lupus peritonitis can generally achieve remission, yet the overall prognosis depends on the presence and severity of multiorgan involvement from SLE. As with any SLE patient, there are also risks of infection from immunosuppression and increased cardiovascular risks.

This patient's evaluation and treatment could have been expedited if he had undergone a paracenteses with determination of the SAAG early in his workup. It is not known why the SAAG was not obtained despite multiple outpatient visits and paracenteses, his history of HBV, and prior alcohol use. This may have been simply an unfortunate oversight. Alternatively, it may have been that his outpatient providers focused on tantalizing clues such as his country of origin, which led to concern for schistosomiasis, and the biopsy findings suggestive of a vascular inflow abnormality that led to further extensive testing. In so doing, the clinicians committed several diagnostic errors, including multiple alternatives bias, anchoring, and confirmation bias.[15] As a result, the patient accrued excess charges of $64,000 from multiple tests, laparoscopic surgery, and 2 hospitalizations. This case highlights how cognitive errors introduce costly variability into patient care, especially when a simple and accurate test is at the beginning of the decision tree.

CLINICAL TEACHING POINTS

1. Diagnostic paracentesis, with calculation of the serum‐ascites albumin gradient, should be the first test in the workup for ascites and can distinguish portal hypertensive causes from nonportal hypertensive causes.
2. Ascites related to SLE can be acute or chronic and caused by bowel infarction, perforation, pancreatitis, mesenteric vasculitis, nephrotic syndrome, heart failure, protein‐losing enteropathy, constrictive pericarditis, lupus peritonitis, Budd‐Chiari syndrome, or serositis (lupus peritonitis).
3. Ascites caused by lupus peritonitis is rare. Once treated, management should be directed toward keeping the SLE in remission.

A 40‐year‐old Sudanese man was admitted due to worsening abdominal pain with recurrent ascites. He had a history of hepatitis B (HBV) infection and diabetes. He previously drank 3 beers per day on the weekends, but he had not consumed alcohol in over a year. He was born in Sudan but lived in Egypt most of his adult life; he immigrated to the United States 6 years previously. He was hospitalized out of state 9 months ago for a swollen abdomen and underwent an exploratory laparotomy that reportedly was unremarkable except for ascites.

Portal hypertension due to liver disease is the most common cause of ascites. This patient has a known risk factor for liver disease (history of HBV infection). Although his reported alcohol consumption is low, there is a synergistic effect on liver injury in the setting of chronic hepatitis. Abdominal pain in the setting of ascites needs to be urgently evaluated to exclude spontaneous bacterial peritonitis (SBP). Also, because chronic HBV infection is the major risk factor for hepatocellular carcinoma in the world, malignant ascites is in the differential. Hepatic vascular thrombosis and tuberculous peritonitis (given the patient's country of origin and travel history) also should be considered. The most appropriate initial test would be a diagnostic paracentesis to support or exclude the presence of SBP and direct the evaluation toward liver disease or other less‐common causes of ascites.

The patient was seen as an outpatient 5 months prior to admission with transient fever and joint pains. Laboratory studies at that visit were notable for a serum albumin of 3.2 g/dL (normal 3.55), 2.4 g of predicted 24‐hour protein on urinalysis (normal <30 mg per 24 hours), creatinine of 0.5 mg/dL (normal 0.81.3), and a positive hepatitis B surface antibody. The working diagnosis was a nonspecific viral syndrome and his symptoms resolved without treatment. One month later, he developed ascites and mild lower extremity edema. Additional laboratory studies at that time showed a normocytic anemia with hemoglobin 11.7 g/dL (normal 13.517.5) and leukopenia with white blood cell count of 2.4 10⁹/L (normal 3.510.5), neutrophil count of 1.45 10⁹/L (normal 1.77.0), and lymphocyte count of 0.58 10⁹/L (normal 0.902.90). Transaminases, serum bilirubin, prothrombin time, alpha fetoprotein, and peripheral blood smear were normal. Human immunodeficiency virus antibody screen and QuantiFERON‐TB assay were negative. Hemoglobin A1c was 6.2% (normal 4.06.0). Repeat urinalysis demonstrated 883 mg of predicted 24‐hour protein. Computed tomography (CT) of the abdomen showed a large amount of intra‐abdominal ascites; the liver and spleen were normal, and there were no varices or other evidence of portal hypertension. Echocardiogram was normal except for a small inferior vena cava (IVC) and a mildly increased right ventricular systolic pressure of 32 mm Hg (systolic blood pressure 98 mm Hg). Due to the indeterminate cause for the patient's ascites, referral was made for gastroenterology evaluation with consideration for a paracentesis.

Cirrhotic ascites seems less likely. Postsinusoidal causes of portal hypertension (eg, cardiomyopathy) are also less likely given the absence of suggestive findings on echocardiography. Malignant ascites also appears less probable in the absence of suggestive findings such as mass lesions, lymphadenopathy, or peritoneal carcinomatosis on CT imaging. The suspicion for tuberculous peritonitis is lower with the negative QuantiFERON‐TB test. Hypoalbuminemia, normocytic anemia, leukopenia, and proteinuria all suggest a systemic inflammatory condition (eg, systemic lupus erythematosus [SLE]) with inflammatory serositis causing ascites). Nephrotic syndrome can cause hypoalbuminemia, edema, and ascites, but his total urine protein losses of <3.5 grams per 24 hours are not in keeping with this diagnosis. Other uncommon causes of ascites such as chylous ascites have not yet been excluded. The most appropriate next step remains ascitic fluid analysis.

A paracentesis yielded 7.8 L of clear‐yellow fluid and improvement in his abdominal discomfort. Analysis showed 224 total nucleated cells/L with 2% neutrophils, 57% lymphocytes, and 37% monocytes. Ascites total protein was 3.8 g/dL and glucose was 55 mg/dL. Gram stain and culture were negative, and cytology was negative for malignancy but showed lymphocytes, plasma cells, monocytes, and reactive mesothelial cells interpreted as consistent with chronic inflammation. The serum‐ascites albumin gradient (SAAG) was not obtained.

With a low leukocyte count and a paucity of neutrophils, this is not SBP. The ascites fluid did not have a chylous appearance. The SAAG, which can distinguish between portal hypertensive and nonportal hypertensive causes for ascites using a cutoff of 1.1 g/dL, was not done. The total protein was high, arguing against cirrhosis. High protein ascites with a high SAAG would suggest a posthepatic source of portal hypertension (eg, Budd‐Chiari syndrome, constrictive pericarditis). High protein ascites with a low SAAG would suggest an inflammatory or malignant source of ascites. The relative lymphocytosis in the ascites fluid suggests an inflammatory process, but is a nonspecific finding. The negative cytology does not completely exclude a malignancy, but given the absence of findings on the CT, malignant ascites is less likely.

Three months before admission, the patient underwent a repeat large‐volume paracentesis and a liver biopsy. The biopsy showed ectopic portal vein branches consistent with hepatoportal sclerosis, but no actual sclerosis was identified. The pathologist concluded that the findings suggested noncirrhotic portal hypertension due to a vascular in‐flow abnormality. Abdominal ultrasound with Doppler was unremarkable other than slightly increased echogenicity of the liver. Magnetic resonance (MR) angiogram showed narrowing of the intra‐abdominal IVC at the level of the diaphragm. Because of concern that hepatic congestion from high pressures in the narrowed IVC was leading to poor vascular inflow as suggested by the biopsy findings, an inferior vena cavagram was performed. This study was normal, although no transhepatic pressure measurements were obtained. Three stool specimens and 2 urine specimens were negative for parasites. The patient required repeat large‐volume paracenteses monthly. SBP was again ruled out, but no other diagnostic labs were obtained. He had anorexia with poor oral intake each time his abdomen became distended.

The patient was started on furosemide 1 month prior to admission to the hospital but had only a slight improvement in the ascites. His other medications included insulin, tamsulosin, and hydrocodone‐acetaminophen. Five days prior to admission, he underwent a diagnostic laparoscopy, which showed only ascites and small adhesions to the anterior abdominal wall. There was no visual evidence of malignancy, and the surgeon commented that the liver was normal. No additional biopsies were obtained.

The liver biopsy findings could be seen in noncirrhotic portal hypertension, although this diagnosis would be unlikely without splenomegaly, varices, or other signs of portal hypertension. However, 2 possible etiologies for noncirrhotic portal hypertension in this patient would be hepatic congestion from the narrowed IVC (although the normal IVC study argues against this) and hepatic schistosomiasis. Schistosomiasis is an important cause of noncirrhotic portal hypertension in endemic areas like this patient's country of origin, but the negative stool and urine studies, combined with the lack of granulomas or fibrosis seen on biopsy, make this condition unlikely.

Systemic amyloidosis (primary or secondary) could also be a cause of ascites and could present with multiorgan involvement (diarrhea and nephrotic syndrome). Amyloid deposits would have probably been seen in the liver biopsy, if present, but may not have been apparent unless specific stains (Congo red) were performed.

Evaluation for systemic, inflammatory autoimmune processes is indicated. Serum autoantibodies (anti‐nuclear antibody [ANA] and extractable nuclear antigens), and a serum and 24‐hour urine protein electrophoresis would be appropriate diagnostic tests. Peritoneal biopsies would have been helpful to assess for serosal diseases.

The patient subsequently developed acute right‐sided abdominal pain requiring urgent evaluation and admission to the hospital. He was initially assessed by a general surgeon, who found no evidence of postoperative complications. His temperature was 36.7C, blood pressure 105/64, heart rate 82, respiratory rate 16, and oxygen saturation 97% on room air. He appeared chronically ill, but he was in no distress and he had a normal mental status. Cardiac exam was normal except for mild jugular venous distension. He had mild bibasilar lung crackles. His abdomen was distended with superficial abdominal tenderness and a fluid wave, but he had normal bowel sounds and no peritoneal signs. He had mild scrotal edema but no peripheral edema. Joint exam did not suggest synovitis and there were no rashes or oral ulcers. Lactate was 0.9 mmol/L (normal 0.62.3), albumin was 2.6 g/dL, and prealbumin was 9 mg/dL (normal 1938). Erythrocyte sedimentation rate and C‐reactive protein were 46 mm/hour (normal <22) and 33.1 mg/L (normal 8), respectively. He had a normocytic anemia and leukopenia. Liver tests and routine chemistries were normal. Serum protein electrophoresis indicated no monoclonal protein. Complete 24‐hour urine collection showed 1.2 g of protein (normal <102 mg). Paracentesis of 3.4 L demonstrated 227 total nucleated cells/L with 2% neutrophils. Following the fluid removal, he had improvement in his pain, which he felt was related to the ascites rather than the recent surgery. Ascites total protein was 3.9 g/dL and ascites albumin was 1.7 g/dL. Ascites culture was negative for infection. Serum Schistosoma immunoglobulin G (IgG) antibody was positive at 3.53 (normal <1.00).

Further history revealed prior episodes of polyarticular joint pain and swelling in his hands and knees 5 years before admission. At that time, he reported a diffuse, pruritic, papular body rash. In addition, he noticed that his fingertips and toes turned white with cold exposure.

Importantly, surgical and infectious complications have been excluded. High protein ascites with a low SAAG of 0.9 suggests an inflammatory source of ascites. The follow‐up clinical data (arthritis, normocytic anemia, leukopenia, rash, Raynaud's phenomenon) suggest a systemic inflammatory syndrome such as SLE, with accompanying serositis. Serologic testing for autoantibodies would be recommended. Peritoneal biopsies, if obtained, may have demonstrated chronic, inflammatory infiltrate (nonspecific) or leukocytoclastic vasculitis (strongly supportive).

ANA enzyme immunoassay was >12 U (normal 1.0 U). Extractable nuclear antigens revealed positive autoantibodies for anti‐SSA, anti‐SSB, and anti‐ribosomal P. Moreover, double‐stranded DNA IgG antibody was 120 IU/mL (normal <30 IU/mL) and C3, C4, and total complement levels were low.

The clinical data support a diagnosis of SLE with serositis. Treatment of the underlying connective tissue disease will typically result in resolution of the ascites; diuretic therapy is generally ineffective.

In consultation with rheumatology and gastroenterology specialists, the diagnosis of SLE was made based on criteria of serositis, persistent leukopenia, arthritis, renal disease (proteinuria), positive ANA, elevated ds‐DNA antibodies, and hypocomplementemia. MR imaging of the abdominal vasculature demonstrated no evidence of vasculitis. The patient was given intravenous methylprednisolone 1 g daily for 3 days followed by high‐dose oral corticosteroids with a gradual taper. He was also started on mycophenolate mofetil as a steroid‐sparing medication (which was later changed to leflunomide due to persistent leukopenia) and hydroxychloroquine. His isolated positive Schistosoma IgG antibody in the absence of other findings was consistent with past exposure or infection. The infectious disease specialist felt there was no evidence of active schistosomiasis, but recommended treatment with a single dose of praziquantel due to the potential benefit with low risk of side effects. The patient had ongoing improvement following dismissal. He had 1 additional paracentesis of 4.1 L, 10 days after his hospitalization, and his ascites and proteinuria resolved. At the 5‐year follow‐up visit, there had been no recurrence of abdominal ascites or abdominal pain. He remains on low‐dose prednisone at 5 mg daily, leflunomide, and hydroxychloroquine.

COMMENTARY

This patient had recurrent ascites with 29.6 L removed over the 4 months prior to admission and an additional 3.4 L during his hospitalization. His outpatient providers initially considered a portal hypertensive etiology of his ascites due to his history of HBV and prior alcohol use. They also appropriately investigated for a possible infectious process. They next directed their evaluation toward the liver biopsy findings, which raised concern for a vascular inflow abnormality. However, the evaluation could have been performed more rapidly and far more cost‐efficiently had a diagnostic paracentesis with calculation of the SAAG been performed early in the evaluation.

The SAAG, which was first described in 1983 by Par and colleagues, is a parameter reflecting the oncotic pressure gradient between the vascular bed and the interstitial splanchnic or ascitic fluid. [1] In the classic study by Runyon and colleagues, a SAAG difference of 1.1 g/dL correctly differentiated causes of ascites due to portal hypertension from those that were not due to portal hypertension 96.7% of the time. [2] Conditions such as nephrotic syndrome, peritoneal carcinomatosis, and serositis (lupus peritonitis) can cause ascites in patients without portal hypertension.

Serositis in the form of pleuritis and/or pericarditis is a common feature of SLE, and ascites has been described in 8% to 11% of SLE patients.[3] However, massive ascites due to lupus peritonitis as a presenting symptom is rare.[4] More common causes of ascites in the setting of SLE include nephrotic syndrome, heart failure, protein‐losing enteropathy, constrictive pericarditis, Budd‐Chiari syndrome, indolent infections such as tuberculosis, and chylous ascites.[5, 6, 7] Of note, lupus peritonitis may be chronic or acute. Chronic ascites develops insidiously with few manifestations of active lupus and may be painless, whereas ascites from acute lupus peritonitis typically develops rapidly and presents with acute abdominal pain and other signs of increased lupus activity.[3, 5, 6, 8, 9]

Ascites from lupus peritonitis may be due to marked serosal exudative accumulation with reduced absorptive capacity in the peritoneum.[3, 4, 10] Other possible causes include peritoneal inflammation from deposition of immune complexes or vasculitis of peritoneal vessels and visceral serous membranes.[4, 9, 11] Although subserosal and submucosal vasculitis have been found in acute ascites, chronic ascites may be related to scarring from vasculitis and serosal inflammation leading to poor venous and lymph drainage.[9] Ascitic fluid characteristics from lupus peritonitis include a SAAG <1.1, presence of white blood cells anywhere in a broad range from 10 to 1630/L, and a range of fluid protein from 3.4 to 4.7 mg/dL.[3] Although not tested in this patient, findings of low complement levels, positive ANA, and elevated anti‐DNA antibody in the ascitic fluid would be supportive of lupus peritonitis, but not specific.[5, 9, 12] Lupus erythematosus cells are occasionally found in the ascitic fluid, but do not rule out other causes of ascites.[9] On retrospective analysis, lupus erythematosus cells were not seen in this patient's pathology specimens.

Treatment of lupus peritonitis and ascites is with high‐dose glucocorticoid therapy, but many patients may need a second immunosuppressant, possibly because of impaired peritoneal circulation from chronic inflammation leading to decreased drug delivery.[13, 14] Chronic ascites may be recalcitrant to systemic glucocorticoids,[3] so a possible alternative therapy is intraperitoneal injection of triamcinolone, which successfully treated massive ascites in a patient who did not respond to oral glucocorticoid treatment.[13] Although ascites may be refractory in some patients, those with chronic lupus peritonitis can generally achieve remission, yet the overall prognosis depends on the presence and severity of multiorgan involvement from SLE. As with any SLE patient, there are also risks of infection from immunosuppression and increased cardiovascular risks.

This patient's evaluation and treatment could have been expedited if he had undergone a paracenteses with determination of the SAAG early in his workup. It is not known why the SAAG was not obtained despite multiple outpatient visits and paracenteses, his history of HBV, and prior alcohol use. This may have been simply an unfortunate oversight. Alternatively, it may have been that his outpatient providers focused on tantalizing clues such as his country of origin, which led to concern for schistosomiasis, and the biopsy findings suggestive of a vascular inflow abnormality that led to further extensive testing. In so doing, the clinicians committed several diagnostic errors, including multiple alternatives bias, anchoring, and confirmation bias.[15] As a result, the patient accrued excess charges of $64,000 from multiple tests, laparoscopic surgery, and 2 hospitalizations. This case highlights how cognitive errors introduce costly variability into patient care, especially when a simple and accurate test is at the beginning of the decision tree.

CLINICAL TEACHING POINTS

1. Diagnostic paracentesis, with calculation of the serum‐ascites albumin gradient, should be the first test in the workup for ascites and can distinguish portal hypertensive causes from nonportal hypertensive causes.
2. Ascites related to SLE can be acute or chronic and caused by bowel infarction, perforation, pancreatitis, mesenteric vasculitis, nephrotic syndrome, heart failure, protein‐losing enteropathy, constrictive pericarditis, lupus peritonitis, Budd‐Chiari syndrome, or serositis (lupus peritonitis).
3. Ascites caused by lupus peritonitis is rare. Once treated, management should be directed toward keeping the SLE in remission.

A 40‐year‐old Sudanese man was admitted due to worsening abdominal pain with recurrent ascites. He had a history of hepatitis B (HBV) infection and diabetes. He previously drank 3 beers per day on the weekends, but he had not consumed alcohol in over a year. He was born in Sudan but lived in Egypt most of his adult life; he immigrated to the United States 6 years previously. He was hospitalized out of state 9 months ago for a swollen abdomen and underwent an exploratory laparotomy that reportedly was unremarkable except for ascites.

Portal hypertension due to liver disease is the most common cause of ascites. This patient has a known risk factor for liver disease (history of HBV infection). Although his reported alcohol consumption is low, there is a synergistic effect on liver injury in the setting of chronic hepatitis. Abdominal pain in the setting of ascites needs to be urgently evaluated to exclude spontaneous bacterial peritonitis (SBP). Also, because chronic HBV infection is the major risk factor for hepatocellular carcinoma in the world, malignant ascites is in the differential. Hepatic vascular thrombosis and tuberculous peritonitis (given the patient's country of origin and travel history) also should be considered. The most appropriate initial test would be a diagnostic paracentesis to support or exclude the presence of SBP and direct the evaluation toward liver disease or other less‐common causes of ascites.

The patient was seen as an outpatient 5 months prior to admission with transient fever and joint pains. Laboratory studies at that visit were notable for a serum albumin of 3.2 g/dL (normal 3.55), 2.4 g of predicted 24‐hour protein on urinalysis (normal <30 mg per 24 hours), creatinine of 0.5 mg/dL (normal 0.81.3), and a positive hepatitis B surface antibody. The working diagnosis was a nonspecific viral syndrome and his symptoms resolved without treatment. One month later, he developed ascites and mild lower extremity edema. Additional laboratory studies at that time showed a normocytic anemia with hemoglobin 11.7 g/dL (normal 13.517.5) and leukopenia with white blood cell count of 2.4 10⁹/L (normal 3.510.5), neutrophil count of 1.45 10⁹/L (normal 1.77.0), and lymphocyte count of 0.58 10⁹/L (normal 0.902.90). Transaminases, serum bilirubin, prothrombin time, alpha fetoprotein, and peripheral blood smear were normal. Human immunodeficiency virus antibody screen and QuantiFERON‐TB assay were negative. Hemoglobin A1c was 6.2% (normal 4.06.0). Repeat urinalysis demonstrated 883 mg of predicted 24‐hour protein. Computed tomography (CT) of the abdomen showed a large amount of intra‐abdominal ascites; the liver and spleen were normal, and there were no varices or other evidence of portal hypertension. Echocardiogram was normal except for a small inferior vena cava (IVC) and a mildly increased right ventricular systolic pressure of 32 mm Hg (systolic blood pressure 98 mm Hg). Due to the indeterminate cause for the patient's ascites, referral was made for gastroenterology evaluation with consideration for a paracentesis.

Cirrhotic ascites seems less likely. Postsinusoidal causes of portal hypertension (eg, cardiomyopathy) are also less likely given the absence of suggestive findings on echocardiography. Malignant ascites also appears less probable in the absence of suggestive findings such as mass lesions, lymphadenopathy, or peritoneal carcinomatosis on CT imaging. The suspicion for tuberculous peritonitis is lower with the negative QuantiFERON‐TB test. Hypoalbuminemia, normocytic anemia, leukopenia, and proteinuria all suggest a systemic inflammatory condition (eg, systemic lupus erythematosus [SLE]) with inflammatory serositis causing ascites). Nephrotic syndrome can cause hypoalbuminemia, edema, and ascites, but his total urine protein losses of <3.5 grams per 24 hours are not in keeping with this diagnosis. Other uncommon causes of ascites such as chylous ascites have not yet been excluded. The most appropriate next step remains ascitic fluid analysis.

A paracentesis yielded 7.8 L of clear‐yellow fluid and improvement in his abdominal discomfort. Analysis showed 224 total nucleated cells/L with 2% neutrophils, 57% lymphocytes, and 37% monocytes. Ascites total protein was 3.8 g/dL and glucose was 55 mg/dL. Gram stain and culture were negative, and cytology was negative for malignancy but showed lymphocytes, plasma cells, monocytes, and reactive mesothelial cells interpreted as consistent with chronic inflammation. The serum‐ascites albumin gradient (SAAG) was not obtained.

With a low leukocyte count and a paucity of neutrophils, this is not SBP. The ascites fluid did not have a chylous appearance. The SAAG, which can distinguish between portal hypertensive and nonportal hypertensive causes for ascites using a cutoff of 1.1 g/dL, was not done. The total protein was high, arguing against cirrhosis. High protein ascites with a high SAAG would suggest a posthepatic source of portal hypertension (eg, Budd‐Chiari syndrome, constrictive pericarditis). High protein ascites with a low SAAG would suggest an inflammatory or malignant source of ascites. The relative lymphocytosis in the ascites fluid suggests an inflammatory process, but is a nonspecific finding. The negative cytology does not completely exclude a malignancy, but given the absence of findings on the CT, malignant ascites is less likely.

Three months before admission, the patient underwent a repeat large‐volume paracentesis and a liver biopsy. The biopsy showed ectopic portal vein branches consistent with hepatoportal sclerosis, but no actual sclerosis was identified. The pathologist concluded that the findings suggested noncirrhotic portal hypertension due to a vascular in‐flow abnormality. Abdominal ultrasound with Doppler was unremarkable other than slightly increased echogenicity of the liver. Magnetic resonance (MR) angiogram showed narrowing of the intra‐abdominal IVC at the level of the diaphragm. Because of concern that hepatic congestion from high pressures in the narrowed IVC was leading to poor vascular inflow as suggested by the biopsy findings, an inferior vena cavagram was performed. This study was normal, although no transhepatic pressure measurements were obtained. Three stool specimens and 2 urine specimens were negative for parasites. The patient required repeat large‐volume paracenteses monthly. SBP was again ruled out, but no other diagnostic labs were obtained. He had anorexia with poor oral intake each time his abdomen became distended.

The patient was started on furosemide 1 month prior to admission to the hospital but had only a slight improvement in the ascites. His other medications included insulin, tamsulosin, and hydrocodone‐acetaminophen. Five days prior to admission, he underwent a diagnostic laparoscopy, which showed only ascites and small adhesions to the anterior abdominal wall. There was no visual evidence of malignancy, and the surgeon commented that the liver was normal. No additional biopsies were obtained.

The liver biopsy findings could be seen in noncirrhotic portal hypertension, although this diagnosis would be unlikely without splenomegaly, varices, or other signs of portal hypertension. However, 2 possible etiologies for noncirrhotic portal hypertension in this patient would be hepatic congestion from the narrowed IVC (although the normal IVC study argues against this) and hepatic schistosomiasis. Schistosomiasis is an important cause of noncirrhotic portal hypertension in endemic areas like this patient's country of origin, but the negative stool and urine studies, combined with the lack of granulomas or fibrosis seen on biopsy, make this condition unlikely.

Systemic amyloidosis (primary or secondary) could also be a cause of ascites and could present with multiorgan involvement (diarrhea and nephrotic syndrome). Amyloid deposits would have probably been seen in the liver biopsy, if present, but may not have been apparent unless specific stains (Congo red) were performed.

Evaluation for systemic, inflammatory autoimmune processes is indicated. Serum autoantibodies (anti‐nuclear antibody [ANA] and extractable nuclear antigens), and a serum and 24‐hour urine protein electrophoresis would be appropriate diagnostic tests. Peritoneal biopsies would have been helpful to assess for serosal diseases.

The patient subsequently developed acute right‐sided abdominal pain requiring urgent evaluation and admission to the hospital. He was initially assessed by a general surgeon, who found no evidence of postoperative complications. His temperature was 36.7C, blood pressure 105/64, heart rate 82, respiratory rate 16, and oxygen saturation 97% on room air. He appeared chronically ill, but he was in no distress and he had a normal mental status. Cardiac exam was normal except for mild jugular venous distension. He had mild bibasilar lung crackles. His abdomen was distended with superficial abdominal tenderness and a fluid wave, but he had normal bowel sounds and no peritoneal signs. He had mild scrotal edema but no peripheral edema. Joint exam did not suggest synovitis and there were no rashes or oral ulcers. Lactate was 0.9 mmol/L (normal 0.62.3), albumin was 2.6 g/dL, and prealbumin was 9 mg/dL (normal 1938). Erythrocyte sedimentation rate and C‐reactive protein were 46 mm/hour (normal <22) and 33.1 mg/L (normal 8), respectively. He had a normocytic anemia and leukopenia. Liver tests and routine chemistries were normal. Serum protein electrophoresis indicated no monoclonal protein. Complete 24‐hour urine collection showed 1.2 g of protein (normal <102 mg). Paracentesis of 3.4 L demonstrated 227 total nucleated cells/L with 2% neutrophils. Following the fluid removal, he had improvement in his pain, which he felt was related to the ascites rather than the recent surgery. Ascites total protein was 3.9 g/dL and ascites albumin was 1.7 g/dL. Ascites culture was negative for infection. Serum Schistosoma immunoglobulin G (IgG) antibody was positive at 3.53 (normal <1.00).

Further history revealed prior episodes of polyarticular joint pain and swelling in his hands and knees 5 years before admission. At that time, he reported a diffuse, pruritic, papular body rash. In addition, he noticed that his fingertips and toes turned white with cold exposure.

Importantly, surgical and infectious complications have been excluded. High protein ascites with a low SAAG of 0.9 suggests an inflammatory source of ascites. The follow‐up clinical data (arthritis, normocytic anemia, leukopenia, rash, Raynaud's phenomenon) suggest a systemic inflammatory syndrome such as SLE, with accompanying serositis. Serologic testing for autoantibodies would be recommended. Peritoneal biopsies, if obtained, may have demonstrated chronic, inflammatory infiltrate (nonspecific) or leukocytoclastic vasculitis (strongly supportive).

ANA enzyme immunoassay was >12 U (normal 1.0 U). Extractable nuclear antigens revealed positive autoantibodies for anti‐SSA, anti‐SSB, and anti‐ribosomal P. Moreover, double‐stranded DNA IgG antibody was 120 IU/mL (normal <30 IU/mL) and C3, C4, and total complement levels were low.

The clinical data support a diagnosis of SLE with serositis. Treatment of the underlying connective tissue disease will typically result in resolution of the ascites; diuretic therapy is generally ineffective.

In consultation with rheumatology and gastroenterology specialists, the diagnosis of SLE was made based on criteria of serositis, persistent leukopenia, arthritis, renal disease (proteinuria), positive ANA, elevated ds‐DNA antibodies, and hypocomplementemia. MR imaging of the abdominal vasculature demonstrated no evidence of vasculitis. The patient was given intravenous methylprednisolone 1 g daily for 3 days followed by high‐dose oral corticosteroids with a gradual taper. He was also started on mycophenolate mofetil as a steroid‐sparing medication (which was later changed to leflunomide due to persistent leukopenia) and hydroxychloroquine. His isolated positive Schistosoma IgG antibody in the absence of other findings was consistent with past exposure or infection. The infectious disease specialist felt there was no evidence of active schistosomiasis, but recommended treatment with a single dose of praziquantel due to the potential benefit with low risk of side effects. The patient had ongoing improvement following dismissal. He had 1 additional paracentesis of 4.1 L, 10 days after his hospitalization, and his ascites and proteinuria resolved. At the 5‐year follow‐up visit, there had been no recurrence of abdominal ascites or abdominal pain. He remains on low‐dose prednisone at 5 mg daily, leflunomide, and hydroxychloroquine.

COMMENTARY

This patient had recurrent ascites with 29.6 L removed over the 4 months prior to admission and an additional 3.4 L during his hospitalization. His outpatient providers initially considered a portal hypertensive etiology of his ascites due to his history of HBV and prior alcohol use. They also appropriately investigated for a possible infectious process. They next directed their evaluation toward the liver biopsy findings, which raised concern for a vascular inflow abnormality. However, the evaluation could have been performed more rapidly and far more cost‐efficiently had a diagnostic paracentesis with calculation of the SAAG been performed early in the evaluation.

The SAAG, which was first described in 1983 by Par and colleagues, is a parameter reflecting the oncotic pressure gradient between the vascular bed and the interstitial splanchnic or ascitic fluid. [1] In the classic study by Runyon and colleagues, a SAAG difference of 1.1 g/dL correctly differentiated causes of ascites due to portal hypertension from those that were not due to portal hypertension 96.7% of the time. [2] Conditions such as nephrotic syndrome, peritoneal carcinomatosis, and serositis (lupus peritonitis) can cause ascites in patients without portal hypertension.

Serositis in the form of pleuritis and/or pericarditis is a common feature of SLE, and ascites has been described in 8% to 11% of SLE patients.[3] However, massive ascites due to lupus peritonitis as a presenting symptom is rare.[4] More common causes of ascites in the setting of SLE include nephrotic syndrome, heart failure, protein‐losing enteropathy, constrictive pericarditis, Budd‐Chiari syndrome, indolent infections such as tuberculosis, and chylous ascites.[5, 6, 7] Of note, lupus peritonitis may be chronic or acute. Chronic ascites develops insidiously with few manifestations of active lupus and may be painless, whereas ascites from acute lupus peritonitis typically develops rapidly and presents with acute abdominal pain and other signs of increased lupus activity.[3, 5, 6, 8, 9]

Ascites from lupus peritonitis may be due to marked serosal exudative accumulation with reduced absorptive capacity in the peritoneum.[3, 4, 10] Other possible causes include peritoneal inflammation from deposition of immune complexes or vasculitis of peritoneal vessels and visceral serous membranes.[4, 9, 11] Although subserosal and submucosal vasculitis have been found in acute ascites, chronic ascites may be related to scarring from vasculitis and serosal inflammation leading to poor venous and lymph drainage.[9] Ascitic fluid characteristics from lupus peritonitis include a SAAG <1.1, presence of white blood cells anywhere in a broad range from 10 to 1630/L, and a range of fluid protein from 3.4 to 4.7 mg/dL.[3] Although not tested in this patient, findings of low complement levels, positive ANA, and elevated anti‐DNA antibody in the ascitic fluid would be supportive of lupus peritonitis, but not specific.[5, 9, 12] Lupus erythematosus cells are occasionally found in the ascitic fluid, but do not rule out other causes of ascites.[9] On retrospective analysis, lupus erythematosus cells were not seen in this patient's pathology specimens.

Treatment of lupus peritonitis and ascites is with high‐dose glucocorticoid therapy, but many patients may need a second immunosuppressant, possibly because of impaired peritoneal circulation from chronic inflammation leading to decreased drug delivery.[13, 14] Chronic ascites may be recalcitrant to systemic glucocorticoids,[3] so a possible alternative therapy is intraperitoneal injection of triamcinolone, which successfully treated massive ascites in a patient who did not respond to oral glucocorticoid treatment.[13] Although ascites may be refractory in some patients, those with chronic lupus peritonitis can generally achieve remission, yet the overall prognosis depends on the presence and severity of multiorgan involvement from SLE. As with any SLE patient, there are also risks of infection from immunosuppression and increased cardiovascular risks.

This patient's evaluation and treatment could have been expedited if he had undergone a paracenteses with determination of the SAAG early in his workup. It is not known why the SAAG was not obtained despite multiple outpatient visits and paracenteses, his history of HBV, and prior alcohol use. This may have been simply an unfortunate oversight. Alternatively, it may have been that his outpatient providers focused on tantalizing clues such as his country of origin, which led to concern for schistosomiasis, and the biopsy findings suggestive of a vascular inflow abnormality that led to further extensive testing. In so doing, the clinicians committed several diagnostic errors, including multiple alternatives bias, anchoring, and confirmation bias.[15] As a result, the patient accrued excess charges of $64,000 from multiple tests, laparoscopic surgery, and 2 hospitalizations. This case highlights how cognitive errors introduce costly variability into patient care, especially when a simple and accurate test is at the beginning of the decision tree.

CLINICAL TEACHING POINTS

1. Diagnostic paracentesis, with calculation of the serum‐ascites albumin gradient, should be the first test in the workup for ascites and can distinguish portal hypertensive causes from nonportal hypertensive causes.
2. Ascites related to SLE can be acute or chronic and caused by bowel infarction, perforation, pancreatitis, mesenteric vasculitis, nephrotic syndrome, heart failure, protein‐losing enteropathy, constrictive pericarditis, lupus peritonitis, Budd‐Chiari syndrome, or serositis (lupus peritonitis).
3. Ascites caused by lupus peritonitis is rare. Once treated, management should be directed toward keeping the SLE in remission.

The decision to transfer a patient to the intensive care unit (ICU) from a general care setting is complex and based not only on clinical findings and patient wishes but also on the understanding that ICU resources are limited and costly.1 Adding to the decision‐making complexity is the knowledge that patients who transfer to an ICU from a general medical unit comprise the highest mortality group of ICU patients, with the mortality rate directly proportional to both the time spent on the general medical unit1, 2 and the number of physiologic abnormalities before ICU admission.3, 4

Prior studies have shown that cardiac arrest and unplanned (unexpected) transfers to the ICU are preceded by a period of physiologic instability reflected in the vital signs.510 However, vital signs alone may not accurately indicate clinical condition. For example, a person may be able to maintain normal blood pressure and heart rate despite severe illness or may have abnormal vital signs at baseline, which may be the case for an otherwise healthy young woman who has baseline low systolic blood pressure. Also, noncritical conditions commonly seen in hospitalized medical or surgical patients, such as anxiety or pain, may increase the respiratory rate or heart rate. Conversely, certain common medications, such as ‐blockers, may mask or blunt the normal physiologic response to illness. Overall, the prevalence of abnormal physiologic variables is high among hospitalized adult patients irrespective of the presence of serious adverse events.11 This prevalence may be a reason why 2 recent studies of inpatient medical emergency teams (METs) or rapid response teams (RRTs), which generally rely on vital signs for activation, failed to show a decrease in adult mortality rates.12, 13

Given the complexity of interpreting single vital sign readings, we evaluated a simple and clinically intuitive variable, the shock index (SI) (heart rate/systolic blood pressure, a noninvasive indication of left ventricular function),14 as a potential marker of the need for intensive care. Allgwer and Burri14 first developed the SI in studies of patients with acute blood loss, intraabdominal bleeding, fat emboli, and severe infections. They observed that a healthy adult had a mean SI of 0.54 (standard deviation [SD], 0.021), while an index of 1.0 indicated threatened shock and indices greater than 1.5 were seen in volume‐deficient shock.

We hypothesized that an elevated SI is a differentiating factor between a patient who had an unplanned ICU transfer and a general medical patient who did not require this higher level of care. To our knowledge, the SI has not been studied for this application previously.

Patients and Methods

Results

A total of 50 pairs of matching cases and controls was included in this study. Table 1 lists the source of admission, demographic characteristics, and numbers of deaths for cases and controls. There were no statistically significant differences in admission source, age, sex, ethnicity, admission care unit, or Charlson Comorbidity Index. Mean length of stay was 14.8 days (SD, 9.7 days) for the cases and 5.7 days (SD, 6.3 days; P < 0.001) for the controls. Admission diagnoses were classified on the basis of the organ system of involvement (Table 2). In 30 of 50 cases, the admission diagnosis and the reason for ICU transfer were related.

We reviewed the vital signs and shock indices for the 24 hours before ICU transfer for each case and over the entire hospitalization for each control, to determine the worst set (the lowest systolic blood pressure and the highest heart rate, respiratory rate, and SI). The cases had 1 to 22 complete sets of vitals for the 24 hours before ICU transfer; the median number of sets was 3 and the mean was 4. The controls had 1 to 12 complete sets for the 24 hours before the worst SI: the median was 3 sets and the mean was 3. In 26 of 50 controls, the worst SI occurred within the first 24 hours after admission. There was a significant difference between the median values of the worst shock indices of the cases and the controls (0.87 vs. 0.72; P < 0.005).

Table 3 shows the different values of the SI and the corresponding odds ratio of unplanned ICU transfer for cases compared with controls. The difference was significant at an SI of 0.85 and greater, indicating a strong association with unplanned ICU transfer.

We also found that the patients who transferred to the ICU had a greater number of inpatient deaths (9 cases vs. 1 control; P = 0.008), which would be expected, but there was no difference in 30‐day or 6‐month mortality rate (Table 1). One patient died after 30 days and while still hospitalized.

Comparison between the temporal trend of vital signs and the SI of the cases for the 24 hours before ICU transfer is shown in Figure 1. This graph shows the median of all the worst values (minimum systolic blood pressure and maximum SI, heart rate, and respiratory rate) over the four 6‐hour time periods (24 hours) preceding ICU transfer. Of note, the change in vital signs is subtle even while the SI increased to more than 0.8 as the patients clinically worsened before transfer.

Figure 1

Discussion

In our comparison of the SI of 50 patients who required unplanned (unexpected) transfer to the ICU with the SI of 50 matched controls who did not require this higher level of care, we found that a SI of 0.85 or greater was significantly associated with unplanned transfer to the ICU. The cases had a significantly higher worst SI than the controls, and they also had a significantly longer hospital stay and higher inpatient mortality rate, as would be expected for a sicker patient population. These findings are important given that the SI may be useful for assessing illness severity, for helping determine the need for transfer to the ICU, or for activating METs or RRTs.

A major problem with providing optimal care for hospitalized general medical patients is the inherent difficulty in determining illness severity and clinical decline, especially when the decline occurs gradually. Existing consensus recommendations for ICU admission include both specific diagnoses and arbitrary objective criteria based on abnormal vital signs and laboratory values.27 Also, individual institutions may have their own ICU admission requirements, which may differ from these or RRT criteria. Although vital signs are important as a snapshot of basic physiologic function, a number of noncritical conditions may lead to abnormal vital signs, and not all abnormal vital signs are associated with an adverse clinical event. By relying solely on vital signs, clinicians may not recognize critical illness and therefore not transfer a patient to the ICU or may inappropriately transfer a patient who does not need ICU‐level care.

Markers of illness severity other than vital signs, such as the Acute Physiology and Chronic Health Evaluation (APACHE) score, have been shown to predict the death of ICU patients17, 18 but have been rarely studied outside the ICU setting.19 Also, calculating the APACHE score is cumbersome, and there is no cutoff score that defines when a patient should be transferred to the ICU. Subbe et al.,20 in their study to identify critically ill patients, found that introduction of a physiological scoring system (including MET or RRT activation scores) would have identified only a small number of additional patients as critically ill. Another common marker of illness severity, the 4 criteria of the systemic inflammatory response syndrome (temperature <36C or >38C; heart rate >90 beats per minute; respiratory rate >20 breaths per minute or PCO₂ <32 mm Hg; and white blood cell count >12,000/L or <4000/L or with more than 10% band cells)21 may be too sensitive to use as a decision aid, since even a healthy person running after a bus could have 2 of the 4 criteria.22 Likewise, surgical patients may have transient leukocytosis due to a stress response independent of an infection.23

The SI may be more accurate than vital signs alone to determine illness severity and who is at risk for an unplanned transfer to the ICU. Birkhahn et al.24 concluded that the SI may be more useful in early hemorrhage than either heart rate or systolic blood pressure alone. Rady et al.25 showed that the SI used in the emergency department can identify critical illness with apparently stable vital signs, where an elevation of the SI above 0.9 was associated with an illness that was treated immediately with admission to the hospital and intensive therapy on admission. However, it is unclear whether the SI can be used to monitor ongoing treatment, because a previous study showed that the SI may be of limited value in the assessment of systemic oxygen transport and response to therapy in clinical septic shock.26 Of note, the SI is mostly independent of the effects of pain or anxiety, which cause a concurrent rise in heart rate and systolic blood pressure. Because the heart's left ventricular work is unchanged or may increase from the underlying catecholamine surge, the SI will be unchanged or may actually decrease.

Our study adds to the medical literature the findings that: (1) the SI may be useful as an indicator of illness severity and a triage tool in patients with no trauma but with various medical conditions, and (2) the SI showed a strong association with unplanned ICU transfer.

The main strength of our study is its case‐control design with matched controls. Also, by comparing groups from the same patient care unit, we sought to minimize the selection bias that can be inherent in case‐control studies. Limitations include the retrospective, nonrandomized study design and the fact that there may have been variations in vital sign measurements by the multiple caregivers. However, the vital signs were taken according to standard hospital practice and reflect real‐world conditions. Although generalizability may be somewhat limited because of our homogeneous patient population, our patients had a wide range of various medical illnesses, so our study should be applicable to other hospital settings, both academic and community‐based.

One of the main weaknesses of our study is that the results were not adjusted for the burden of comorbid conditions, although there were no statistically significant differences in the number of comorbid conditions among the cases and the controls (P = 0.96). Also, we did not directly compare the SI with vital signs alone to determine superiority.

The SI may be an important objective measure to help clinicians decide when patients need treatment that is more aggressive, assistance from a MET or an RRT, or a preemptive, rather than unplanned, transfer to an ICU. Although it is unlikely that a single measure will allow accurate triage of all medical or surgical patients, the SI may be a useful adjunct to clinical judgment and other objective measures in determining illness severity and clinical decline. Further prospective studies are needed to compare the role of the SI specifically with MET or RRT activation criteria, to clarify the role of comorbid conditions in unplanned transfers to the ICU, to validate the cut point for the SI in various disease states, and to assess its utility in patients with septic shock. Depending on these results, it may be beneficial to incorporate the SI into the electronic medical record as an automatic alert to identify patients at risk for ICU transfer.

Conclusions

The SI is an easily calculated composite index of heart rate and systolic blood pressure. An elevated SI of 0.85 can identify patients who are at risk for unplanned transfer to the ICU from general patient care units. Future studies will determine whether the SI is more accurate than simple vital signs as an indicator of clinical decline. If so, it may be useful as a trigger to activate METs or RRTs for treatment.

The decision to transfer a patient to the intensive care unit (ICU) from a general care setting is complex and based not only on clinical findings and patient wishes but also on the understanding that ICU resources are limited and costly.1 Adding to the decision‐making complexity is the knowledge that patients who transfer to an ICU from a general medical unit comprise the highest mortality group of ICU patients, with the mortality rate directly proportional to both the time spent on the general medical unit1, 2 and the number of physiologic abnormalities before ICU admission.3, 4

Prior studies have shown that cardiac arrest and unplanned (unexpected) transfers to the ICU are preceded by a period of physiologic instability reflected in the vital signs.510 However, vital signs alone may not accurately indicate clinical condition. For example, a person may be able to maintain normal blood pressure and heart rate despite severe illness or may have abnormal vital signs at baseline, which may be the case for an otherwise healthy young woman who has baseline low systolic blood pressure. Also, noncritical conditions commonly seen in hospitalized medical or surgical patients, such as anxiety or pain, may increase the respiratory rate or heart rate. Conversely, certain common medications, such as ‐blockers, may mask or blunt the normal physiologic response to illness. Overall, the prevalence of abnormal physiologic variables is high among hospitalized adult patients irrespective of the presence of serious adverse events.11 This prevalence may be a reason why 2 recent studies of inpatient medical emergency teams (METs) or rapid response teams (RRTs), which generally rely on vital signs for activation, failed to show a decrease in adult mortality rates.12, 13

Given the complexity of interpreting single vital sign readings, we evaluated a simple and clinically intuitive variable, the shock index (SI) (heart rate/systolic blood pressure, a noninvasive indication of left ventricular function),14 as a potential marker of the need for intensive care. Allgwer and Burri14 first developed the SI in studies of patients with acute blood loss, intraabdominal bleeding, fat emboli, and severe infections. They observed that a healthy adult had a mean SI of 0.54 (standard deviation [SD], 0.021), while an index of 1.0 indicated threatened shock and indices greater than 1.5 were seen in volume‐deficient shock.

We hypothesized that an elevated SI is a differentiating factor between a patient who had an unplanned ICU transfer and a general medical patient who did not require this higher level of care. To our knowledge, the SI has not been studied for this application previously.

Patients and Methods

Results

A total of 50 pairs of matching cases and controls was included in this study. Table 1 lists the source of admission, demographic characteristics, and numbers of deaths for cases and controls. There were no statistically significant differences in admission source, age, sex, ethnicity, admission care unit, or Charlson Comorbidity Index. Mean length of stay was 14.8 days (SD, 9.7 days) for the cases and 5.7 days (SD, 6.3 days; P < 0.001) for the controls. Admission diagnoses were classified on the basis of the organ system of involvement (Table 2). In 30 of 50 cases, the admission diagnosis and the reason for ICU transfer were related.

We reviewed the vital signs and shock indices for the 24 hours before ICU transfer for each case and over the entire hospitalization for each control, to determine the worst set (the lowest systolic blood pressure and the highest heart rate, respiratory rate, and SI). The cases had 1 to 22 complete sets of vitals for the 24 hours before ICU transfer; the median number of sets was 3 and the mean was 4. The controls had 1 to 12 complete sets for the 24 hours before the worst SI: the median was 3 sets and the mean was 3. In 26 of 50 controls, the worst SI occurred within the first 24 hours after admission. There was a significant difference between the median values of the worst shock indices of the cases and the controls (0.87 vs. 0.72; P < 0.005).

Table 3 shows the different values of the SI and the corresponding odds ratio of unplanned ICU transfer for cases compared with controls. The difference was significant at an SI of 0.85 and greater, indicating a strong association with unplanned ICU transfer.

We also found that the patients who transferred to the ICU had a greater number of inpatient deaths (9 cases vs. 1 control; P = 0.008), which would be expected, but there was no difference in 30‐day or 6‐month mortality rate (Table 1). One patient died after 30 days and while still hospitalized.

Comparison between the temporal trend of vital signs and the SI of the cases for the 24 hours before ICU transfer is shown in Figure 1. This graph shows the median of all the worst values (minimum systolic blood pressure and maximum SI, heart rate, and respiratory rate) over the four 6‐hour time periods (24 hours) preceding ICU transfer. Of note, the change in vital signs is subtle even while the SI increased to more than 0.8 as the patients clinically worsened before transfer.

Figure 1

Discussion

In our comparison of the SI of 50 patients who required unplanned (unexpected) transfer to the ICU with the SI of 50 matched controls who did not require this higher level of care, we found that a SI of 0.85 or greater was significantly associated with unplanned transfer to the ICU. The cases had a significantly higher worst SI than the controls, and they also had a significantly longer hospital stay and higher inpatient mortality rate, as would be expected for a sicker patient population. These findings are important given that the SI may be useful for assessing illness severity, for helping determine the need for transfer to the ICU, or for activating METs or RRTs.

A major problem with providing optimal care for hospitalized general medical patients is the inherent difficulty in determining illness severity and clinical decline, especially when the decline occurs gradually. Existing consensus recommendations for ICU admission include both specific diagnoses and arbitrary objective criteria based on abnormal vital signs and laboratory values.27 Also, individual institutions may have their own ICU admission requirements, which may differ from these or RRT criteria. Although vital signs are important as a snapshot of basic physiologic function, a number of noncritical conditions may lead to abnormal vital signs, and not all abnormal vital signs are associated with an adverse clinical event. By relying solely on vital signs, clinicians may not recognize critical illness and therefore not transfer a patient to the ICU or may inappropriately transfer a patient who does not need ICU‐level care.

Markers of illness severity other than vital signs, such as the Acute Physiology and Chronic Health Evaluation (APACHE) score, have been shown to predict the death of ICU patients17, 18 but have been rarely studied outside the ICU setting.19 Also, calculating the APACHE score is cumbersome, and there is no cutoff score that defines when a patient should be transferred to the ICU. Subbe et al.,20 in their study to identify critically ill patients, found that introduction of a physiological scoring system (including MET or RRT activation scores) would have identified only a small number of additional patients as critically ill. Another common marker of illness severity, the 4 criteria of the systemic inflammatory response syndrome (temperature <36C or >38C; heart rate >90 beats per minute; respiratory rate >20 breaths per minute or PCO₂ <32 mm Hg; and white blood cell count >12,000/L or <4000/L or with more than 10% band cells)21 may be too sensitive to use as a decision aid, since even a healthy person running after a bus could have 2 of the 4 criteria.22 Likewise, surgical patients may have transient leukocytosis due to a stress response independent of an infection.23

The SI may be more accurate than vital signs alone to determine illness severity and who is at risk for an unplanned transfer to the ICU. Birkhahn et al.24 concluded that the SI may be more useful in early hemorrhage than either heart rate or systolic blood pressure alone. Rady et al.25 showed that the SI used in the emergency department can identify critical illness with apparently stable vital signs, where an elevation of the SI above 0.9 was associated with an illness that was treated immediately with admission to the hospital and intensive therapy on admission. However, it is unclear whether the SI can be used to monitor ongoing treatment, because a previous study showed that the SI may be of limited value in the assessment of systemic oxygen transport and response to therapy in clinical septic shock.26 Of note, the SI is mostly independent of the effects of pain or anxiety, which cause a concurrent rise in heart rate and systolic blood pressure. Because the heart's left ventricular work is unchanged or may increase from the underlying catecholamine surge, the SI will be unchanged or may actually decrease.

Our study adds to the medical literature the findings that: (1) the SI may be useful as an indicator of illness severity and a triage tool in patients with no trauma but with various medical conditions, and (2) the SI showed a strong association with unplanned ICU transfer.

The main strength of our study is its case‐control design with matched controls. Also, by comparing groups from the same patient care unit, we sought to minimize the selection bias that can be inherent in case‐control studies. Limitations include the retrospective, nonrandomized study design and the fact that there may have been variations in vital sign measurements by the multiple caregivers. However, the vital signs were taken according to standard hospital practice and reflect real‐world conditions. Although generalizability may be somewhat limited because of our homogeneous patient population, our patients had a wide range of various medical illnesses, so our study should be applicable to other hospital settings, both academic and community‐based.

One of the main weaknesses of our study is that the results were not adjusted for the burden of comorbid conditions, although there were no statistically significant differences in the number of comorbid conditions among the cases and the controls (P = 0.96). Also, we did not directly compare the SI with vital signs alone to determine superiority.

The SI may be an important objective measure to help clinicians decide when patients need treatment that is more aggressive, assistance from a MET or an RRT, or a preemptive, rather than unplanned, transfer to an ICU. Although it is unlikely that a single measure will allow accurate triage of all medical or surgical patients, the SI may be a useful adjunct to clinical judgment and other objective measures in determining illness severity and clinical decline. Further prospective studies are needed to compare the role of the SI specifically with MET or RRT activation criteria, to clarify the role of comorbid conditions in unplanned transfers to the ICU, to validate the cut point for the SI in various disease states, and to assess its utility in patients with septic shock. Depending on these results, it may be beneficial to incorporate the SI into the electronic medical record as an automatic alert to identify patients at risk for ICU transfer.

Conclusions

The SI is an easily calculated composite index of heart rate and systolic blood pressure. An elevated SI of 0.85 can identify patients who are at risk for unplanned transfer to the ICU from general patient care units. Future studies will determine whether the SI is more accurate than simple vital signs as an indicator of clinical decline. If so, it may be useful as a trigger to activate METs or RRTs for treatment.

The decision to transfer a patient to the intensive care unit (ICU) from a general care setting is complex and based not only on clinical findings and patient wishes but also on the understanding that ICU resources are limited and costly.1 Adding to the decision‐making complexity is the knowledge that patients who transfer to an ICU from a general medical unit comprise the highest mortality group of ICU patients, with the mortality rate directly proportional to both the time spent on the general medical unit1, 2 and the number of physiologic abnormalities before ICU admission.3, 4

Prior studies have shown that cardiac arrest and unplanned (unexpected) transfers to the ICU are preceded by a period of physiologic instability reflected in the vital signs.510 However, vital signs alone may not accurately indicate clinical condition. For example, a person may be able to maintain normal blood pressure and heart rate despite severe illness or may have abnormal vital signs at baseline, which may be the case for an otherwise healthy young woman who has baseline low systolic blood pressure. Also, noncritical conditions commonly seen in hospitalized medical or surgical patients, such as anxiety or pain, may increase the respiratory rate or heart rate. Conversely, certain common medications, such as ‐blockers, may mask or blunt the normal physiologic response to illness. Overall, the prevalence of abnormal physiologic variables is high among hospitalized adult patients irrespective of the presence of serious adverse events.11 This prevalence may be a reason why 2 recent studies of inpatient medical emergency teams (METs) or rapid response teams (RRTs), which generally rely on vital signs for activation, failed to show a decrease in adult mortality rates.12, 13

Given the complexity of interpreting single vital sign readings, we evaluated a simple and clinically intuitive variable, the shock index (SI) (heart rate/systolic blood pressure, a noninvasive indication of left ventricular function),14 as a potential marker of the need for intensive care. Allgwer and Burri14 first developed the SI in studies of patients with acute blood loss, intraabdominal bleeding, fat emboli, and severe infections. They observed that a healthy adult had a mean SI of 0.54 (standard deviation [SD], 0.021), while an index of 1.0 indicated threatened shock and indices greater than 1.5 were seen in volume‐deficient shock.

We hypothesized that an elevated SI is a differentiating factor between a patient who had an unplanned ICU transfer and a general medical patient who did not require this higher level of care. To our knowledge, the SI has not been studied for this application previously.

Patients and Methods

Results

A total of 50 pairs of matching cases and controls was included in this study. Table 1 lists the source of admission, demographic characteristics, and numbers of deaths for cases and controls. There were no statistically significant differences in admission source, age, sex, ethnicity, admission care unit, or Charlson Comorbidity Index. Mean length of stay was 14.8 days (SD, 9.7 days) for the cases and 5.7 days (SD, 6.3 days; P < 0.001) for the controls. Admission diagnoses were classified on the basis of the organ system of involvement (Table 2). In 30 of 50 cases, the admission diagnosis and the reason for ICU transfer were related.

We reviewed the vital signs and shock indices for the 24 hours before ICU transfer for each case and over the entire hospitalization for each control, to determine the worst set (the lowest systolic blood pressure and the highest heart rate, respiratory rate, and SI). The cases had 1 to 22 complete sets of vitals for the 24 hours before ICU transfer; the median number of sets was 3 and the mean was 4. The controls had 1 to 12 complete sets for the 24 hours before the worst SI: the median was 3 sets and the mean was 3. In 26 of 50 controls, the worst SI occurred within the first 24 hours after admission. There was a significant difference between the median values of the worst shock indices of the cases and the controls (0.87 vs. 0.72; P < 0.005).

Table 3 shows the different values of the SI and the corresponding odds ratio of unplanned ICU transfer for cases compared with controls. The difference was significant at an SI of 0.85 and greater, indicating a strong association with unplanned ICU transfer.

We also found that the patients who transferred to the ICU had a greater number of inpatient deaths (9 cases vs. 1 control; P = 0.008), which would be expected, but there was no difference in 30‐day or 6‐month mortality rate (Table 1). One patient died after 30 days and while still hospitalized.

Comparison between the temporal trend of vital signs and the SI of the cases for the 24 hours before ICU transfer is shown in Figure 1. This graph shows the median of all the worst values (minimum systolic blood pressure and maximum SI, heart rate, and respiratory rate) over the four 6‐hour time periods (24 hours) preceding ICU transfer. Of note, the change in vital signs is subtle even while the SI increased to more than 0.8 as the patients clinically worsened before transfer.

Figure 1

Discussion

In our comparison of the SI of 50 patients who required unplanned (unexpected) transfer to the ICU with the SI of 50 matched controls who did not require this higher level of care, we found that a SI of 0.85 or greater was significantly associated with unplanned transfer to the ICU. The cases had a significantly higher worst SI than the controls, and they also had a significantly longer hospital stay and higher inpatient mortality rate, as would be expected for a sicker patient population. These findings are important given that the SI may be useful for assessing illness severity, for helping determine the need for transfer to the ICU, or for activating METs or RRTs.

A major problem with providing optimal care for hospitalized general medical patients is the inherent difficulty in determining illness severity and clinical decline, especially when the decline occurs gradually. Existing consensus recommendations for ICU admission include both specific diagnoses and arbitrary objective criteria based on abnormal vital signs and laboratory values.27 Also, individual institutions may have their own ICU admission requirements, which may differ from these or RRT criteria. Although vital signs are important as a snapshot of basic physiologic function, a number of noncritical conditions may lead to abnormal vital signs, and not all abnormal vital signs are associated with an adverse clinical event. By relying solely on vital signs, clinicians may not recognize critical illness and therefore not transfer a patient to the ICU or may inappropriately transfer a patient who does not need ICU‐level care.

Markers of illness severity other than vital signs, such as the Acute Physiology and Chronic Health Evaluation (APACHE) score, have been shown to predict the death of ICU patients17, 18 but have been rarely studied outside the ICU setting.19 Also, calculating the APACHE score is cumbersome, and there is no cutoff score that defines when a patient should be transferred to the ICU. Subbe et al.,20 in their study to identify critically ill patients, found that introduction of a physiological scoring system (including MET or RRT activation scores) would have identified only a small number of additional patients as critically ill. Another common marker of illness severity, the 4 criteria of the systemic inflammatory response syndrome (temperature <36C or >38C; heart rate >90 beats per minute; respiratory rate >20 breaths per minute or PCO₂ <32 mm Hg; and white blood cell count >12,000/L or <4000/L or with more than 10% band cells)21 may be too sensitive to use as a decision aid, since even a healthy person running after a bus could have 2 of the 4 criteria.22 Likewise, surgical patients may have transient leukocytosis due to a stress response independent of an infection.23

The SI may be more accurate than vital signs alone to determine illness severity and who is at risk for an unplanned transfer to the ICU. Birkhahn et al.24 concluded that the SI may be more useful in early hemorrhage than either heart rate or systolic blood pressure alone. Rady et al.25 showed that the SI used in the emergency department can identify critical illness with apparently stable vital signs, where an elevation of the SI above 0.9 was associated with an illness that was treated immediately with admission to the hospital and intensive therapy on admission. However, it is unclear whether the SI can be used to monitor ongoing treatment, because a previous study showed that the SI may be of limited value in the assessment of systemic oxygen transport and response to therapy in clinical septic shock.26 Of note, the SI is mostly independent of the effects of pain or anxiety, which cause a concurrent rise in heart rate and systolic blood pressure. Because the heart's left ventricular work is unchanged or may increase from the underlying catecholamine surge, the SI will be unchanged or may actually decrease.

Our study adds to the medical literature the findings that: (1) the SI may be useful as an indicator of illness severity and a triage tool in patients with no trauma but with various medical conditions, and (2) the SI showed a strong association with unplanned ICU transfer.

The main strength of our study is its case‐control design with matched controls. Also, by comparing groups from the same patient care unit, we sought to minimize the selection bias that can be inherent in case‐control studies. Limitations include the retrospective, nonrandomized study design and the fact that there may have been variations in vital sign measurements by the multiple caregivers. However, the vital signs were taken according to standard hospital practice and reflect real‐world conditions. Although generalizability may be somewhat limited because of our homogeneous patient population, our patients had a wide range of various medical illnesses, so our study should be applicable to other hospital settings, both academic and community‐based.

One of the main weaknesses of our study is that the results were not adjusted for the burden of comorbid conditions, although there were no statistically significant differences in the number of comorbid conditions among the cases and the controls (P = 0.96). Also, we did not directly compare the SI with vital signs alone to determine superiority.

The SI may be an important objective measure to help clinicians decide when patients need treatment that is more aggressive, assistance from a MET or an RRT, or a preemptive, rather than unplanned, transfer to an ICU. Although it is unlikely that a single measure will allow accurate triage of all medical or surgical patients, the SI may be a useful adjunct to clinical judgment and other objective measures in determining illness severity and clinical decline. Further prospective studies are needed to compare the role of the SI specifically with MET or RRT activation criteria, to clarify the role of comorbid conditions in unplanned transfers to the ICU, to validate the cut point for the SI in various disease states, and to assess its utility in patients with septic shock. Depending on these results, it may be beneficial to incorporate the SI into the electronic medical record as an automatic alert to identify patients at risk for ICU transfer.

Conclusions

The SI is an easily calculated composite index of heart rate and systolic blood pressure. An elevated SI of 0.85 can identify patients who are at risk for unplanned transfer to the ICU from general patient care units. Future studies will determine whether the SI is more accurate than simple vital signs as an indicator of clinical decline. If so, it may be useful as a trigger to activate METs or RRTs for treatment.

Severe sepsis and septic shock account for more than 750,000 hospital admissions and 215,000 deaths per year.1 Early fluid resuscitation is the cornerstone of treatment, and early goal‐directed therapy (EGDT), which includes a target central venous pressure (CVP) of 8 to 12 mm Hg, has been shown to improve outcomes, including mortality and length of stay.2 This goal allows appropriate initial resuscitation and may decrease the risk of excess fluid administration, which is related to adverse outcomes in critically ill patients.3 However, nonintensivists may not start early aggressive fluid resuscitation because of inability to accurately assess intravascular volume, concerns for inadvertent volume overload, or the difficulty of recognizing insidious illness. Assessment of volume status, primarily from inspection of the internal jugular vein to estimate CVP, is difficult to perform by clinical examination alone, especially if CVP is very low.4 Inspection of the external jugular vein is perhaps easier than inspecting the internal jugular vein and appears to accurately estimate CVP,5 but it does not allow the degree of precision necessary for EGDT. Echocardiography can estimate CVP based on respirophasic variation or collapsibility index, but this technique requires expensive equipment and sonographic expertise. The current gold standard technique for measuring CVP requires an invasive central venous catheter, which can delay timely resuscitation and is associated with complications.6

An alternative technique to guide resuscitation efforts should be accurate, safe, rapid, and easy to perform at the bedside, while providing real‐time measurement results. We hypothesized that CVP can be accurately assessed using noninvasive ultrasound imaging of the internal jugular vein, since jugular venous pressure is essentially equal to CVP.7 Specifically, our study estimated the diagnostic accuracy of ultrasound measurement of the aspect ratio (height/width) of the internal jugular vein compared with the invasively measured CVP target for EGDT. We expected that a lower aspect ratio would correlate with a lower CVP and a higher aspect ratio would correlate with a higher CVP.

Methods

Volunteers were enrolled at Saint Mary's Hospital (Mayo Clinic) in Rochester, MN, from January to March 2006, and patients were enrolled at Saint Mary's Hospital and at Abbott Northwestern Hospital (Allina Hospitals and Clinics) in Minneapolis, MN, from May 2006 to October 2007. The study was approved by the Institutional Review Boards of Mayo Clinic and Allina and had 2 phases. The first phase comprised ultrasound measurements of internal jugular vein aspect ratio and determination of intraobserver and interobserver agreement in healthy volunteers. The second phase involved measurement of internal jugular vein aspect ratio and invasive CVP in a convenience sample of 44 spontaneously breathing patients admitted to medical intensive care units: 9 patients at Saint Marys Hospital and 35 patients at Abbott Northwestern Hospital. Patients were enrolled only when study members were on duty in the intensive care unit and able to perform study measurements. As a result, a high proportion of patients who may have been eligible were not asked to participate.

Each volunteer was deemed euvolemic on the basis of normal orthostatic measurements and normal oral intake with no vomiting or diarrhea in the previous 5 days. Measurements of 19 volunteers were made by 1 author (A.S.K.), with subsequent measurements of 15 of the volunteers made by another author (O.G.) to determine interobserver variability; 4 participants did not undergo a second measurement because of scheduling conflicts.

Inclusion and exclusion criteria for the critically ill patients are provided in Table 1. Recruitment was based on presenting symptoms and test results that led the intensive care unit physicians to decide to place a CVP monitor. All the enrolled patients had invasive CVP measurement performed approximately 30 to 40 minutes after ultrasound measurement of the internal jugular vein; this delay was the time required to place the central line and obtain the measurement. All patients who were invited to participate in the study were included. No patients were excluded on the basis of the exclusion criteria or because of inability to place a central line. No complications related to central line placement occurred.

We followed a prescribed measurement technique (Table 2) to determine the internal jugular vein aspect ratio in all volunteers and patients. Measurements of the volunteers were made with a Site‐Rite 3 Ultrasound System (Bard Access Systems, Inc., Salt Lake City, UT) using a 9.0‐MHz transducer. Measurements of the critically ill patients were made with a SonoSite MicroMaxx ultrasound system (SonoSite, Inc., Bothell, WA) using a 10.5‐MHz transducer. Study team physicians initially were blinded to actual measured CVP. Internal jugular vein aspect ratio and CVP were measured at tidal volume end‐expiration for all patients. One measurement was obtained for each patient, with measurements being made by 1 of 4 physicians (2 intensivists, 1 critical care fellow, and 1 chief medicine resident). With no specific ultrasound training and with only minimal practice, the physicians could obtain the optimal aspect ratio within a few seconds (Figure 1).

Figure 1

This was an exploratory prospective study, and all methods of data collection were designed before patient enrollment. However, the ultrasound‐derived aspect ratio of 0.83 (which defined a CVP of 8 mm Hg) was determined post hoc to maximize sensitivity and specificity and was based on the aspect ratio of the euvolemic volunteers and the inflection point of the CVP vs aspect ratio curve for the critically ill patients.

Results

We first evaluated 19 white volunteers: 12 women and 7 men. Mean (SD) age was 42 (11) years and mean body mass index was 26.6 (4.5) kg/m². Mean arterial pressure was 89 (13) mm Hg and mean heart rate was 71 (15) beats/minute. Mean aspect ratio of the right and left internal jugular vein for all volunteers was 0.82 (0.07). There was no difference in aspect ratio between the right (0.83 [0.10]) and left (0.81 [0.13]) vein (P > 0.10). Also, no difference in the aspect ratio was seen between men (0.81 [0.08]) and women (0.83 [0.07]) (P = 0.77). Bland‐Altman analysis indicated moderate intraobserver and interobserver agreement for the aspect ratio measurements (Figure 2).

Figure 2

We then compared the aspect ratio measured using ultrasound and CVP measured with an invasive monitor for 44 spontaneously breathing critically ill patients (22 women and 22 men; 38 were white). Mean (SD) age was 66 (14) years and mean body mass index was 28.8 (9.1) kg/m². Mean arterial pressure (n = 36) was 67 (12) mm Hg and mean heart rate (n = 34) was 92 (22) beats/minute. Systemic inflammatory response syndrome (SIRS) criteria were present in 23 of 40 patients; complete data were unavailable for the other 4 patients. Of these 40 patients, 20 had sepsis, 15 had severe sepsis, and 5 had septic shock. The most common diagnoses were gastrointestinal tract bleeding in 6 patients and congestive heart failure in 4 patients. Acute Physiology and Chronic Health Evaluation (APACHE III) score, available for 8 of the 9 patients at Saint Marys Hospital, was 63 (10).

Figure 3 shows measured aspect ratios vs. invasively measured CVP for the critically ill patients. The curvilinear result is consistent with venous and right ventricular compliance ( volume/ pressure) characteristics. Note that the inflection point (beginning of the increased slope) of the curve corresponds to a CVP of about 8 mm Hg. Furthermore, the aspect ratio (0.8) at this point is the same as that seen in the euvolemic volunteers. These findings suggest that, in spontaneously breathing patients, a CVP of about 8 mm Hg and an aspect ratio of about 0.8 each defines the beginning of the plateau on the cardiac Frank‐Starling curve.

Figure 3

Ultrasound imaging of the internal jugular vein aspect ratio accurately estimated the CVP target of 8 mm Hg based on the area under the receiver operating characteristics curve of 0.84 (95% confidence interval [CI], 0.72‐0.96) (Figure 4). For an invasively measured CVP of less than 8 mm Hg, the likelihood ratio for a positive ultrasound test result (aspect ratio < 0.83) was 3.5 (95% CI, 1.4‐8.4) and for a negative test result (aspect ratio 0.83) was 0.30 (95% CI, 0.14‐0.62). Clinically, this means that patients with a measured aspect ratio of less than 0.83 require further fluid resuscitation, whereas patients with a measured aspect ratio of 0.83 or greater are less likely to benefit from fluid resuscitation.

Figure 4

Discussion

This study demonstrated that the EGDT CVP target of 8 to 12 mm Hg can be accurately estimated (referenced to invasive CVP monitoring) using noninvasive ultrasound measurement of the internal jugular vein in spontaneously breathing critically ill patients. The measurement process is simple to perform at the bedside and moderately reliable when performed by different observers; also, the results appear to be equivalent for both sides and for males or females. Images can be stored electronically for serial comparisons and for viewing by other caregivers. Because the aspect ratio is essentially constant over the length of the internal jugular vein, unlike diameter, measurements can be performed anywhere along the vein. Also, ultrasound imaging allows visualization of the internal jugular vein despite anatomic variation.9

Previous attempts at noninvasive hemodynamic monitoring using plethysmography, thoracic electrical bioimpedance, and external Doppler probes have shown these methods to be cumbersome or inaccurate.1013 Other investigators have used echocardiography14, 15 and handheld ultrasound16 to image the diameter of the inferior vena cava in order to assess intravascular volume status, but these techniques require expertise in sonographic imaging. An alternative technique is to measure peripheral venous pressure, which correlates with CVP.17 This method, however, requires technical expertise to zero the monitor and is not yet widely used for critically ill patients. A literature search found 1 letter to the editor suggesting that real‐time ultrasound imaging of the internal jugular vein could be used to qualitatively determine jugular venous pressure18 and 3 studies using ultrasound in conjunction with a pressure transducer or manometer to determine the pressure needed to collapse the vein (either the internal jugular or a peripheral vein), with subsequent correlation to CVP.1921 These latter techniques appear to be cumbersome and require custom equipment that is not readily available in most hospitals.

Any measurement of CVP, including our technique, assumes correlation with volume responsiveness as a surrogate for intravascular volume. However, CVP is governed by multiple physiologic and pathologic factors, including intravascular volume, vascular and ventricular compliance, ventricular function, tricuspid stenosis and regurgitation, cardiac tamponade, and atrioventricular dissociation.22, 23 Therefore, CVP alone may not be an accurate measure of volume responsiveness (intravascular volume). CVP may also have spontaneous variation similar to pulmonary capillary wedge pressure, which can be as high as 7 mm Hg in any given patient.24 Furthermore, invasive CVP monitors also have limitations, and the overall accuracy of the Philips system used at Saint Marys Hospital is 4% of the reading or 4 mm Hg, whichever is greater.25 Nonetheless, the EGDT algorithm that incorporates CVP measurement with a target of 8 to 12 mm Hg in spontaneously breathing patients and 12 mm Hg in mechanically ventilated patients has resulted in decreased mortality among patients with severe sepsis and is recommended by the Surviving Sepsis Campaign guidelines26 and the Institute for Healthcare Improvement.27

These study results are important because nonintensivists such as hospitalists and emergency department physicians can use this technique to provide rapid fluid resuscitation early in the course of severe sepsis and septic shock, when aggressive fluid resuscitation is most effective. Ultrasound imaging of the internal jugular vein is easy to perform without formal training, and the equipment is readily available in most hospitals. Future studies will evaluate outcomes in spontaneously breathing and ventilated patients to determine the accuracy of this measurement technique in volume‐depleted and volume‐overloaded states. If validated in different patient populations, ultrasound measurement of the internal jugular vein could substitute for the EGDT CVP target in critically ill patients and allow early aggressive fluid resuscitation before a central venous catheter is placed.

Severe sepsis and septic shock account for more than 750,000 hospital admissions and 215,000 deaths per year.1 Early fluid resuscitation is the cornerstone of treatment, and early goal‐directed therapy (EGDT), which includes a target central venous pressure (CVP) of 8 to 12 mm Hg, has been shown to improve outcomes, including mortality and length of stay.2 This goal allows appropriate initial resuscitation and may decrease the risk of excess fluid administration, which is related to adverse outcomes in critically ill patients.3 However, nonintensivists may not start early aggressive fluid resuscitation because of inability to accurately assess intravascular volume, concerns for inadvertent volume overload, or the difficulty of recognizing insidious illness. Assessment of volume status, primarily from inspection of the internal jugular vein to estimate CVP, is difficult to perform by clinical examination alone, especially if CVP is very low.4 Inspection of the external jugular vein is perhaps easier than inspecting the internal jugular vein and appears to accurately estimate CVP,5 but it does not allow the degree of precision necessary for EGDT. Echocardiography can estimate CVP based on respirophasic variation or collapsibility index, but this technique requires expensive equipment and sonographic expertise. The current gold standard technique for measuring CVP requires an invasive central venous catheter, which can delay timely resuscitation and is associated with complications.6

An alternative technique to guide resuscitation efforts should be accurate, safe, rapid, and easy to perform at the bedside, while providing real‐time measurement results. We hypothesized that CVP can be accurately assessed using noninvasive ultrasound imaging of the internal jugular vein, since jugular venous pressure is essentially equal to CVP.7 Specifically, our study estimated the diagnostic accuracy of ultrasound measurement of the aspect ratio (height/width) of the internal jugular vein compared with the invasively measured CVP target for EGDT. We expected that a lower aspect ratio would correlate with a lower CVP and a higher aspect ratio would correlate with a higher CVP.

Methods

Volunteers were enrolled at Saint Mary's Hospital (Mayo Clinic) in Rochester, MN, from January to March 2006, and patients were enrolled at Saint Mary's Hospital and at Abbott Northwestern Hospital (Allina Hospitals and Clinics) in Minneapolis, MN, from May 2006 to October 2007. The study was approved by the Institutional Review Boards of Mayo Clinic and Allina and had 2 phases. The first phase comprised ultrasound measurements of internal jugular vein aspect ratio and determination of intraobserver and interobserver agreement in healthy volunteers. The second phase involved measurement of internal jugular vein aspect ratio and invasive CVP in a convenience sample of 44 spontaneously breathing patients admitted to medical intensive care units: 9 patients at Saint Marys Hospital and 35 patients at Abbott Northwestern Hospital. Patients were enrolled only when study members were on duty in the intensive care unit and able to perform study measurements. As a result, a high proportion of patients who may have been eligible were not asked to participate.

Each volunteer was deemed euvolemic on the basis of normal orthostatic measurements and normal oral intake with no vomiting or diarrhea in the previous 5 days. Measurements of 19 volunteers were made by 1 author (A.S.K.), with subsequent measurements of 15 of the volunteers made by another author (O.G.) to determine interobserver variability; 4 participants did not undergo a second measurement because of scheduling conflicts.

Inclusion and exclusion criteria for the critically ill patients are provided in Table 1. Recruitment was based on presenting symptoms and test results that led the intensive care unit physicians to decide to place a CVP monitor. All the enrolled patients had invasive CVP measurement performed approximately 30 to 40 minutes after ultrasound measurement of the internal jugular vein; this delay was the time required to place the central line and obtain the measurement. All patients who were invited to participate in the study were included. No patients were excluded on the basis of the exclusion criteria or because of inability to place a central line. No complications related to central line placement occurred.

We followed a prescribed measurement technique (Table 2) to determine the internal jugular vein aspect ratio in all volunteers and patients. Measurements of the volunteers were made with a Site‐Rite 3 Ultrasound System (Bard Access Systems, Inc., Salt Lake City, UT) using a 9.0‐MHz transducer. Measurements of the critically ill patients were made with a SonoSite MicroMaxx ultrasound system (SonoSite, Inc., Bothell, WA) using a 10.5‐MHz transducer. Study team physicians initially were blinded to actual measured CVP. Internal jugular vein aspect ratio and CVP were measured at tidal volume end‐expiration for all patients. One measurement was obtained for each patient, with measurements being made by 1 of 4 physicians (2 intensivists, 1 critical care fellow, and 1 chief medicine resident). With no specific ultrasound training and with only minimal practice, the physicians could obtain the optimal aspect ratio within a few seconds (Figure 1).

Figure 1

This was an exploratory prospective study, and all methods of data collection were designed before patient enrollment. However, the ultrasound‐derived aspect ratio of 0.83 (which defined a CVP of 8 mm Hg) was determined post hoc to maximize sensitivity and specificity and was based on the aspect ratio of the euvolemic volunteers and the inflection point of the CVP vs aspect ratio curve for the critically ill patients.

Results

We first evaluated 19 white volunteers: 12 women and 7 men. Mean (SD) age was 42 (11) years and mean body mass index was 26.6 (4.5) kg/m². Mean arterial pressure was 89 (13) mm Hg and mean heart rate was 71 (15) beats/minute. Mean aspect ratio of the right and left internal jugular vein for all volunteers was 0.82 (0.07). There was no difference in aspect ratio between the right (0.83 [0.10]) and left (0.81 [0.13]) vein (P > 0.10). Also, no difference in the aspect ratio was seen between men (0.81 [0.08]) and women (0.83 [0.07]) (P = 0.77). Bland‐Altman analysis indicated moderate intraobserver and interobserver agreement for the aspect ratio measurements (Figure 2).

Figure 2

We then compared the aspect ratio measured using ultrasound and CVP measured with an invasive monitor for 44 spontaneously breathing critically ill patients (22 women and 22 men; 38 were white). Mean (SD) age was 66 (14) years and mean body mass index was 28.8 (9.1) kg/m². Mean arterial pressure (n = 36) was 67 (12) mm Hg and mean heart rate (n = 34) was 92 (22) beats/minute. Systemic inflammatory response syndrome (SIRS) criteria were present in 23 of 40 patients; complete data were unavailable for the other 4 patients. Of these 40 patients, 20 had sepsis, 15 had severe sepsis, and 5 had septic shock. The most common diagnoses were gastrointestinal tract bleeding in 6 patients and congestive heart failure in 4 patients. Acute Physiology and Chronic Health Evaluation (APACHE III) score, available for 8 of the 9 patients at Saint Marys Hospital, was 63 (10).

Figure 3 shows measured aspect ratios vs. invasively measured CVP for the critically ill patients. The curvilinear result is consistent with venous and right ventricular compliance ( volume/ pressure) characteristics. Note that the inflection point (beginning of the increased slope) of the curve corresponds to a CVP of about 8 mm Hg. Furthermore, the aspect ratio (0.8) at this point is the same as that seen in the euvolemic volunteers. These findings suggest that, in spontaneously breathing patients, a CVP of about 8 mm Hg and an aspect ratio of about 0.8 each defines the beginning of the plateau on the cardiac Frank‐Starling curve.

Figure 3

Ultrasound imaging of the internal jugular vein aspect ratio accurately estimated the CVP target of 8 mm Hg based on the area under the receiver operating characteristics curve of 0.84 (95% confidence interval [CI], 0.72‐0.96) (Figure 4). For an invasively measured CVP of less than 8 mm Hg, the likelihood ratio for a positive ultrasound test result (aspect ratio < 0.83) was 3.5 (95% CI, 1.4‐8.4) and for a negative test result (aspect ratio 0.83) was 0.30 (95% CI, 0.14‐0.62). Clinically, this means that patients with a measured aspect ratio of less than 0.83 require further fluid resuscitation, whereas patients with a measured aspect ratio of 0.83 or greater are less likely to benefit from fluid resuscitation.

Figure 4

Discussion

This study demonstrated that the EGDT CVP target of 8 to 12 mm Hg can be accurately estimated (referenced to invasive CVP monitoring) using noninvasive ultrasound measurement of the internal jugular vein in spontaneously breathing critically ill patients. The measurement process is simple to perform at the bedside and moderately reliable when performed by different observers; also, the results appear to be equivalent for both sides and for males or females. Images can be stored electronically for serial comparisons and for viewing by other caregivers. Because the aspect ratio is essentially constant over the length of the internal jugular vein, unlike diameter, measurements can be performed anywhere along the vein. Also, ultrasound imaging allows visualization of the internal jugular vein despite anatomic variation.9

Previous attempts at noninvasive hemodynamic monitoring using plethysmography, thoracic electrical bioimpedance, and external Doppler probes have shown these methods to be cumbersome or inaccurate.1013 Other investigators have used echocardiography14, 15 and handheld ultrasound16 to image the diameter of the inferior vena cava in order to assess intravascular volume status, but these techniques require expertise in sonographic imaging. An alternative technique is to measure peripheral venous pressure, which correlates with CVP.17 This method, however, requires technical expertise to zero the monitor and is not yet widely used for critically ill patients. A literature search found 1 letter to the editor suggesting that real‐time ultrasound imaging of the internal jugular vein could be used to qualitatively determine jugular venous pressure18 and 3 studies using ultrasound in conjunction with a pressure transducer or manometer to determine the pressure needed to collapse the vein (either the internal jugular or a peripheral vein), with subsequent correlation to CVP.1921 These latter techniques appear to be cumbersome and require custom equipment that is not readily available in most hospitals.

Any measurement of CVP, including our technique, assumes correlation with volume responsiveness as a surrogate for intravascular volume. However, CVP is governed by multiple physiologic and pathologic factors, including intravascular volume, vascular and ventricular compliance, ventricular function, tricuspid stenosis and regurgitation, cardiac tamponade, and atrioventricular dissociation.22, 23 Therefore, CVP alone may not be an accurate measure of volume responsiveness (intravascular volume). CVP may also have spontaneous variation similar to pulmonary capillary wedge pressure, which can be as high as 7 mm Hg in any given patient.24 Furthermore, invasive CVP monitors also have limitations, and the overall accuracy of the Philips system used at Saint Marys Hospital is 4% of the reading or 4 mm Hg, whichever is greater.25 Nonetheless, the EGDT algorithm that incorporates CVP measurement with a target of 8 to 12 mm Hg in spontaneously breathing patients and 12 mm Hg in mechanically ventilated patients has resulted in decreased mortality among patients with severe sepsis and is recommended by the Surviving Sepsis Campaign guidelines26 and the Institute for Healthcare Improvement.27

These study results are important because nonintensivists such as hospitalists and emergency department physicians can use this technique to provide rapid fluid resuscitation early in the course of severe sepsis and septic shock, when aggressive fluid resuscitation is most effective. Ultrasound imaging of the internal jugular vein is easy to perform without formal training, and the equipment is readily available in most hospitals. Future studies will evaluate outcomes in spontaneously breathing and ventilated patients to determine the accuracy of this measurement technique in volume‐depleted and volume‐overloaded states. If validated in different patient populations, ultrasound measurement of the internal jugular vein could substitute for the EGDT CVP target in critically ill patients and allow early aggressive fluid resuscitation before a central venous catheter is placed.

Severe sepsis and septic shock account for more than 750,000 hospital admissions and 215,000 deaths per year.1 Early fluid resuscitation is the cornerstone of treatment, and early goal‐directed therapy (EGDT), which includes a target central venous pressure (CVP) of 8 to 12 mm Hg, has been shown to improve outcomes, including mortality and length of stay.2 This goal allows appropriate initial resuscitation and may decrease the risk of excess fluid administration, which is related to adverse outcomes in critically ill patients.3 However, nonintensivists may not start early aggressive fluid resuscitation because of inability to accurately assess intravascular volume, concerns for inadvertent volume overload, or the difficulty of recognizing insidious illness. Assessment of volume status, primarily from inspection of the internal jugular vein to estimate CVP, is difficult to perform by clinical examination alone, especially if CVP is very low.4 Inspection of the external jugular vein is perhaps easier than inspecting the internal jugular vein and appears to accurately estimate CVP,5 but it does not allow the degree of precision necessary for EGDT. Echocardiography can estimate CVP based on respirophasic variation or collapsibility index, but this technique requires expensive equipment and sonographic expertise. The current gold standard technique for measuring CVP requires an invasive central venous catheter, which can delay timely resuscitation and is associated with complications.6

An alternative technique to guide resuscitation efforts should be accurate, safe, rapid, and easy to perform at the bedside, while providing real‐time measurement results. We hypothesized that CVP can be accurately assessed using noninvasive ultrasound imaging of the internal jugular vein, since jugular venous pressure is essentially equal to CVP.7 Specifically, our study estimated the diagnostic accuracy of ultrasound measurement of the aspect ratio (height/width) of the internal jugular vein compared with the invasively measured CVP target for EGDT. We expected that a lower aspect ratio would correlate with a lower CVP and a higher aspect ratio would correlate with a higher CVP.

Methods

Volunteers were enrolled at Saint Mary's Hospital (Mayo Clinic) in Rochester, MN, from January to March 2006, and patients were enrolled at Saint Mary's Hospital and at Abbott Northwestern Hospital (Allina Hospitals and Clinics) in Minneapolis, MN, from May 2006 to October 2007. The study was approved by the Institutional Review Boards of Mayo Clinic and Allina and had 2 phases. The first phase comprised ultrasound measurements of internal jugular vein aspect ratio and determination of intraobserver and interobserver agreement in healthy volunteers. The second phase involved measurement of internal jugular vein aspect ratio and invasive CVP in a convenience sample of 44 spontaneously breathing patients admitted to medical intensive care units: 9 patients at Saint Marys Hospital and 35 patients at Abbott Northwestern Hospital. Patients were enrolled only when study members were on duty in the intensive care unit and able to perform study measurements. As a result, a high proportion of patients who may have been eligible were not asked to participate.

Each volunteer was deemed euvolemic on the basis of normal orthostatic measurements and normal oral intake with no vomiting or diarrhea in the previous 5 days. Measurements of 19 volunteers were made by 1 author (A.S.K.), with subsequent measurements of 15 of the volunteers made by another author (O.G.) to determine interobserver variability; 4 participants did not undergo a second measurement because of scheduling conflicts.

Inclusion and exclusion criteria for the critically ill patients are provided in Table 1. Recruitment was based on presenting symptoms and test results that led the intensive care unit physicians to decide to place a CVP monitor. All the enrolled patients had invasive CVP measurement performed approximately 30 to 40 minutes after ultrasound measurement of the internal jugular vein; this delay was the time required to place the central line and obtain the measurement. All patients who were invited to participate in the study were included. No patients were excluded on the basis of the exclusion criteria or because of inability to place a central line. No complications related to central line placement occurred.

We followed a prescribed measurement technique (Table 2) to determine the internal jugular vein aspect ratio in all volunteers and patients. Measurements of the volunteers were made with a Site‐Rite 3 Ultrasound System (Bard Access Systems, Inc., Salt Lake City, UT) using a 9.0‐MHz transducer. Measurements of the critically ill patients were made with a SonoSite MicroMaxx ultrasound system (SonoSite, Inc., Bothell, WA) using a 10.5‐MHz transducer. Study team physicians initially were blinded to actual measured CVP. Internal jugular vein aspect ratio and CVP were measured at tidal volume end‐expiration for all patients. One measurement was obtained for each patient, with measurements being made by 1 of 4 physicians (2 intensivists, 1 critical care fellow, and 1 chief medicine resident). With no specific ultrasound training and with only minimal practice, the physicians could obtain the optimal aspect ratio within a few seconds (Figure 1).

Figure 1

This was an exploratory prospective study, and all methods of data collection were designed before patient enrollment. However, the ultrasound‐derived aspect ratio of 0.83 (which defined a CVP of 8 mm Hg) was determined post hoc to maximize sensitivity and specificity and was based on the aspect ratio of the euvolemic volunteers and the inflection point of the CVP vs aspect ratio curve for the critically ill patients.

Results

We first evaluated 19 white volunteers: 12 women and 7 men. Mean (SD) age was 42 (11) years and mean body mass index was 26.6 (4.5) kg/m². Mean arterial pressure was 89 (13) mm Hg and mean heart rate was 71 (15) beats/minute. Mean aspect ratio of the right and left internal jugular vein for all volunteers was 0.82 (0.07). There was no difference in aspect ratio between the right (0.83 [0.10]) and left (0.81 [0.13]) vein (P > 0.10). Also, no difference in the aspect ratio was seen between men (0.81 [0.08]) and women (0.83 [0.07]) (P = 0.77). Bland‐Altman analysis indicated moderate intraobserver and interobserver agreement for the aspect ratio measurements (Figure 2).

Figure 2

We then compared the aspect ratio measured using ultrasound and CVP measured with an invasive monitor for 44 spontaneously breathing critically ill patients (22 women and 22 men; 38 were white). Mean (SD) age was 66 (14) years and mean body mass index was 28.8 (9.1) kg/m². Mean arterial pressure (n = 36) was 67 (12) mm Hg and mean heart rate (n = 34) was 92 (22) beats/minute. Systemic inflammatory response syndrome (SIRS) criteria were present in 23 of 40 patients; complete data were unavailable for the other 4 patients. Of these 40 patients, 20 had sepsis, 15 had severe sepsis, and 5 had septic shock. The most common diagnoses were gastrointestinal tract bleeding in 6 patients and congestive heart failure in 4 patients. Acute Physiology and Chronic Health Evaluation (APACHE III) score, available for 8 of the 9 patients at Saint Marys Hospital, was 63 (10).

Figure 3 shows measured aspect ratios vs. invasively measured CVP for the critically ill patients. The curvilinear result is consistent with venous and right ventricular compliance ( volume/ pressure) characteristics. Note that the inflection point (beginning of the increased slope) of the curve corresponds to a CVP of about 8 mm Hg. Furthermore, the aspect ratio (0.8) at this point is the same as that seen in the euvolemic volunteers. These findings suggest that, in spontaneously breathing patients, a CVP of about 8 mm Hg and an aspect ratio of about 0.8 each defines the beginning of the plateau on the cardiac Frank‐Starling curve.

Figure 3

Ultrasound imaging of the internal jugular vein aspect ratio accurately estimated the CVP target of 8 mm Hg based on the area under the receiver operating characteristics curve of 0.84 (95% confidence interval [CI], 0.72‐0.96) (Figure 4). For an invasively measured CVP of less than 8 mm Hg, the likelihood ratio for a positive ultrasound test result (aspect ratio < 0.83) was 3.5 (95% CI, 1.4‐8.4) and for a negative test result (aspect ratio 0.83) was 0.30 (95% CI, 0.14‐0.62). Clinically, this means that patients with a measured aspect ratio of less than 0.83 require further fluid resuscitation, whereas patients with a measured aspect ratio of 0.83 or greater are less likely to benefit from fluid resuscitation.

Figure 4

Discussion

This study demonstrated that the EGDT CVP target of 8 to 12 mm Hg can be accurately estimated (referenced to invasive CVP monitoring) using noninvasive ultrasound measurement of the internal jugular vein in spontaneously breathing critically ill patients. The measurement process is simple to perform at the bedside and moderately reliable when performed by different observers; also, the results appear to be equivalent for both sides and for males or females. Images can be stored electronically for serial comparisons and for viewing by other caregivers. Because the aspect ratio is essentially constant over the length of the internal jugular vein, unlike diameter, measurements can be performed anywhere along the vein. Also, ultrasound imaging allows visualization of the internal jugular vein despite anatomic variation.9

Previous attempts at noninvasive hemodynamic monitoring using plethysmography, thoracic electrical bioimpedance, and external Doppler probes have shown these methods to be cumbersome or inaccurate.1013 Other investigators have used echocardiography14, 15 and handheld ultrasound16 to image the diameter of the inferior vena cava in order to assess intravascular volume status, but these techniques require expertise in sonographic imaging. An alternative technique is to measure peripheral venous pressure, which correlates with CVP.17 This method, however, requires technical expertise to zero the monitor and is not yet widely used for critically ill patients. A literature search found 1 letter to the editor suggesting that real‐time ultrasound imaging of the internal jugular vein could be used to qualitatively determine jugular venous pressure18 and 3 studies using ultrasound in conjunction with a pressure transducer or manometer to determine the pressure needed to collapse the vein (either the internal jugular or a peripheral vein), with subsequent correlation to CVP.1921 These latter techniques appear to be cumbersome and require custom equipment that is not readily available in most hospitals.

Any measurement of CVP, including our technique, assumes correlation with volume responsiveness as a surrogate for intravascular volume. However, CVP is governed by multiple physiologic and pathologic factors, including intravascular volume, vascular and ventricular compliance, ventricular function, tricuspid stenosis and regurgitation, cardiac tamponade, and atrioventricular dissociation.22, 23 Therefore, CVP alone may not be an accurate measure of volume responsiveness (intravascular volume). CVP may also have spontaneous variation similar to pulmonary capillary wedge pressure, which can be as high as 7 mm Hg in any given patient.24 Furthermore, invasive CVP monitors also have limitations, and the overall accuracy of the Philips system used at Saint Marys Hospital is 4% of the reading or 4 mm Hg, whichever is greater.25 Nonetheless, the EGDT algorithm that incorporates CVP measurement with a target of 8 to 12 mm Hg in spontaneously breathing patients and 12 mm Hg in mechanically ventilated patients has resulted in decreased mortality among patients with severe sepsis and is recommended by the Surviving Sepsis Campaign guidelines26 and the Institute for Healthcare Improvement.27

These study results are important because nonintensivists such as hospitalists and emergency department physicians can use this technique to provide rapid fluid resuscitation early in the course of severe sepsis and septic shock, when aggressive fluid resuscitation is most effective. Ultrasound imaging of the internal jugular vein is easy to perform without formal training, and the equipment is readily available in most hospitals. Future studies will evaluate outcomes in spontaneously breathing and ventilated patients to determine the accuracy of this measurement technique in volume‐depleted and volume‐overloaded states. If validated in different patient populations, ultrasound measurement of the internal jugular vein could substitute for the EGDT CVP target in critically ill patients and allow early aggressive fluid resuscitation before a central venous catheter is placed.

Hospitalized patients are often debilitated, either from their admitting illness or from the deconditioning that occurs with inactivity. Functional decline, which appears to progress in a hierarchical pattern,1 occurs in 24% to 50% of geriatric patients during hospitalization and is poorly documented.2 Such a decline is associated not only with longer hospital stays and increased health care costs but also with higher mortality.3 The American College of Physicians, through its Assessing Care of Vulnerable Elders project, expressly endorsed gait and mobility evaluation as a quality indicator, and examination insufficiency is well documented.4

Of the several existing mobility assessment tools, few are used routinely in hospital. Some require complex scoring; others require timing and/or a trained occupational therapist.5 We created a simplified tool named Independent Mobility Validation Examination (I‐MOVE) for use by bedside caregivers. We evaluated the tool's face validity and interobserver agreement.

I‐MOVE

I‐MOVE, represented schematically in Figure 1, is a performance test that assesses the patient's ability to perform a sequence of 6 basic tasks: rolling over in bed, sitting up, standing, transferring to a chair, walking in the room, and walking in the hallway. Most motor functions can be assumed to be hierarchical in nature; any patient who can perform at the highest level, such as walking safely, also would be expected to perform at the lowest level.

Figure 1

Instructions for administering I‐MOVE are as follows:

• 1

  Review current orders. Exclude patients ordered on bed rest or non‐weight‐bearing or other orders precluding any of the 6 requested actions.

• 2

  Prepare environment.
• a

  Chair at bedside.

• b

  Lower side bed rail closest to chair.

• c

  Clear path for patient to ambulate.

• d

  Ensure patient dons slippers.

• e

  Flatten bed.

• f

  Ensure any gait assistive device, if generally used by the patient, is within reach from the bedside.

• 3

  Requests for patient action (for steps c through f, make available and within reach any appropriate gait‐assistance device such as walker or cane, if such is customarily used at home or newly prescribed):
• a

  With patient lying supine in bed, with close supervision, ask patient to turn from side to side in bed (request when both bed rails are up).

• b

  Lower side rail closer to chair and ask the patient to rise up to a sitting position and turn to sit up with legs dangling off the bed.

• c

  Ask the patient to stand.

• d

  Ask the patient to take a seat in the chair next to the bed.

• e

  Ask the patient to ambulate in the room.

• f

  Ask the patient to ambulate in the hallway.

• 4

  At any point if the patient seems incapable, unsteady, or unsafe to accomplish the requested task, render hands‐on assistance and immediately end the test.

• 5

  Document, by number (1‐12), the activity level successfully accomplished independently by the patient (even number levels) or accomplished with assistance (odd number levels).

• 6

  Patient may be considered independent if able to perform the activity with a normal assistive device (cane, walker, brace, or crutches) but not using furniture.

• 7

  Assistance is defined as any physical contact with the patient.

Findings

Face Validity

We sent surveys to 6 experienced practicing clinicians at our hospital: a geriatrician, a physiatrist, an exercise physiologist, an occupational therapist, a physical therapist, and a registered nurse. We asked each clinician to rate the 6 I‐MOVE elements (requested actions) for clinical relevance to mobility independence. Relevance of each element was measured on an ordinal scale with scores ranging from 1 to 4, with: 1 not relevant; 2 somewhat relevant; 3 quite relevant; and 4 very relevant. From the 5 responses we received, 4 evaluators ranked all 6 I‐MOVE requested actions as very relevant. The fifth evaluator ranked 5 of the 6 actions as very relevant and 1 action (walking in the room) as quite relevant. These results demonstrate general agreement that I‐MOVE is, at face value, a reasonable measure of independent mobility.

Interrater Reliability

The protocol was approved by the hospital's institutional review board. On a general medical unita non‐electrocardiographic telemetry, nonsurgical unit of an acute care hospital, where patients are assigned the primary service of an internal medicine physicianwe instructed 2 registered nurse (RN) volunteers (RN1 and RN2) in the I‐MOVE protocol. Each RN administered I‐MOVE independently to 41 consecutive, cognitively intact patients in a blinded fashion (ie, neither nurse was aware of the other's scoring of each patient) and within 1 hour of each other's assessment.

After administering I‐MOVE to each patient, the nurse judged and scored the patient's performance using the 12‐level I‐MOVE ordinal scale, ranging from a low value of 1, complete dependence, to the highest value of 12, complete independence. The patients' I‐MOVE score pairs recorded by RN1 and RN2 were statistically compared. Interrater reliability, a comparison of the 41 patients' score pairs, is graphically represented in Figure 2. The calculated intraclass correlation coefficient (r) was 0.90, indicating excellent agreement (r > 0.75).

Figure 2

Discussion

Traditional physical examinations by physicians and assessments by nurses do not routinely extend to standardized mobility testing and may fail to recognize disability. Of the existing mobility assessment tools, we believe that most are not suited to patients hospitalized on general medical units. I‐MOVE has been designed to address this need, with an emphasis on practicality and brevity to allow repetition at appropriate intervals (tracking), as is done for vital signs. In this initial study, I‐MOVE was found to have face‐valid content and excellent interrater agreement.

Our study had several limitations. Only 1 pair of test administrators was involved; the sample population was chosen by convenience; clustering of outcomes occurred at level 12, which may have augmented the agreement; and the study was limited to cognitively intact patients. Note that we chose to use the intraclass correlation coefficient rather than the statistic because the weighting between the ordinal I‐MOVE scores has not yet been studied and defined. Also, the weighted is asymptotically equivalent to the intraclass correlation coefficient.

I‐MOVE is intended to aid caregivers in the recognition of debility so that appropriate interventions such as physical therapy may be prescribed. It was designed to complement, not replace, specialized evaluations such as those performed by physical therapists, occupational therapists, or comprehensive geriatric assessments. This practical assessment of basic functioning may enhance communication among caregivers, patients, and patients' family members, especially with regard to discharge planning. Further study is needed to validate I‐MOVE against existing tools, evaluate I‐MOVE's utility as a vital sign, and discern whether a sharp or unexpected decline portends a medical complication.

Hospitalized patients are often debilitated, either from their admitting illness or from the deconditioning that occurs with inactivity. Functional decline, which appears to progress in a hierarchical pattern,1 occurs in 24% to 50% of geriatric patients during hospitalization and is poorly documented.2 Such a decline is associated not only with longer hospital stays and increased health care costs but also with higher mortality.3 The American College of Physicians, through its Assessing Care of Vulnerable Elders project, expressly endorsed gait and mobility evaluation as a quality indicator, and examination insufficiency is well documented.4

Of the several existing mobility assessment tools, few are used routinely in hospital. Some require complex scoring; others require timing and/or a trained occupational therapist.5 We created a simplified tool named Independent Mobility Validation Examination (I‐MOVE) for use by bedside caregivers. We evaluated the tool's face validity and interobserver agreement.

I‐MOVE

I‐MOVE, represented schematically in Figure 1, is a performance test that assesses the patient's ability to perform a sequence of 6 basic tasks: rolling over in bed, sitting up, standing, transferring to a chair, walking in the room, and walking in the hallway. Most motor functions can be assumed to be hierarchical in nature; any patient who can perform at the highest level, such as walking safely, also would be expected to perform at the lowest level.

Figure 1

Instructions for administering I‐MOVE are as follows:

• 1

  Review current orders. Exclude patients ordered on bed rest or non‐weight‐bearing or other orders precluding any of the 6 requested actions.

• 2

  Prepare environment.
• a

  Chair at bedside.

• b

  Lower side bed rail closest to chair.

• c

  Clear path for patient to ambulate.

• d

  Ensure patient dons slippers.

• e

  Flatten bed.

• f

  Ensure any gait assistive device, if generally used by the patient, is within reach from the bedside.

• 3

  Requests for patient action (for steps c through f, make available and within reach any appropriate gait‐assistance device such as walker or cane, if such is customarily used at home or newly prescribed):
• a

  With patient lying supine in bed, with close supervision, ask patient to turn from side to side in bed (request when both bed rails are up).

• b

  Lower side rail closer to chair and ask the patient to rise up to a sitting position and turn to sit up with legs dangling off the bed.

• c

  Ask the patient to stand.

• d

  Ask the patient to take a seat in the chair next to the bed.

• e

  Ask the patient to ambulate in the room.

• f

  Ask the patient to ambulate in the hallway.

• 4

  At any point if the patient seems incapable, unsteady, or unsafe to accomplish the requested task, render hands‐on assistance and immediately end the test.

• 5

  Document, by number (1‐12), the activity level successfully accomplished independently by the patient (even number levels) or accomplished with assistance (odd number levels).

• 6

  Patient may be considered independent if able to perform the activity with a normal assistive device (cane, walker, brace, or crutches) but not using furniture.

• 7

  Assistance is defined as any physical contact with the patient.

Findings

Face Validity

We sent surveys to 6 experienced practicing clinicians at our hospital: a geriatrician, a physiatrist, an exercise physiologist, an occupational therapist, a physical therapist, and a registered nurse. We asked each clinician to rate the 6 I‐MOVE elements (requested actions) for clinical relevance to mobility independence. Relevance of each element was measured on an ordinal scale with scores ranging from 1 to 4, with: 1 not relevant; 2 somewhat relevant; 3 quite relevant; and 4 very relevant. From the 5 responses we received, 4 evaluators ranked all 6 I‐MOVE requested actions as very relevant. The fifth evaluator ranked 5 of the 6 actions as very relevant and 1 action (walking in the room) as quite relevant. These results demonstrate general agreement that I‐MOVE is, at face value, a reasonable measure of independent mobility.

Interrater Reliability

The protocol was approved by the hospital's institutional review board. On a general medical unita non‐electrocardiographic telemetry, nonsurgical unit of an acute care hospital, where patients are assigned the primary service of an internal medicine physicianwe instructed 2 registered nurse (RN) volunteers (RN1 and RN2) in the I‐MOVE protocol. Each RN administered I‐MOVE independently to 41 consecutive, cognitively intact patients in a blinded fashion (ie, neither nurse was aware of the other's scoring of each patient) and within 1 hour of each other's assessment.

After administering I‐MOVE to each patient, the nurse judged and scored the patient's performance using the 12‐level I‐MOVE ordinal scale, ranging from a low value of 1, complete dependence, to the highest value of 12, complete independence. The patients' I‐MOVE score pairs recorded by RN1 and RN2 were statistically compared. Interrater reliability, a comparison of the 41 patients' score pairs, is graphically represented in Figure 2. The calculated intraclass correlation coefficient (r) was 0.90, indicating excellent agreement (r > 0.75).

Figure 2

Discussion

Traditional physical examinations by physicians and assessments by nurses do not routinely extend to standardized mobility testing and may fail to recognize disability. Of the existing mobility assessment tools, we believe that most are not suited to patients hospitalized on general medical units. I‐MOVE has been designed to address this need, with an emphasis on practicality and brevity to allow repetition at appropriate intervals (tracking), as is done for vital signs. In this initial study, I‐MOVE was found to have face‐valid content and excellent interrater agreement.

Our study had several limitations. Only 1 pair of test administrators was involved; the sample population was chosen by convenience; clustering of outcomes occurred at level 12, which may have augmented the agreement; and the study was limited to cognitively intact patients. Note that we chose to use the intraclass correlation coefficient rather than the statistic because the weighting between the ordinal I‐MOVE scores has not yet been studied and defined. Also, the weighted is asymptotically equivalent to the intraclass correlation coefficient.

I‐MOVE is intended to aid caregivers in the recognition of debility so that appropriate interventions such as physical therapy may be prescribed. It was designed to complement, not replace, specialized evaluations such as those performed by physical therapists, occupational therapists, or comprehensive geriatric assessments. This practical assessment of basic functioning may enhance communication among caregivers, patients, and patients' family members, especially with regard to discharge planning. Further study is needed to validate I‐MOVE against existing tools, evaluate I‐MOVE's utility as a vital sign, and discern whether a sharp or unexpected decline portends a medical complication.

Hospitalized patients are often debilitated, either from their admitting illness or from the deconditioning that occurs with inactivity. Functional decline, which appears to progress in a hierarchical pattern,1 occurs in 24% to 50% of geriatric patients during hospitalization and is poorly documented.2 Such a decline is associated not only with longer hospital stays and increased health care costs but also with higher mortality.3 The American College of Physicians, through its Assessing Care of Vulnerable Elders project, expressly endorsed gait and mobility evaluation as a quality indicator, and examination insufficiency is well documented.4

Of the several existing mobility assessment tools, few are used routinely in hospital. Some require complex scoring; others require timing and/or a trained occupational therapist.5 We created a simplified tool named Independent Mobility Validation Examination (I‐MOVE) for use by bedside caregivers. We evaluated the tool's face validity and interobserver agreement.

I‐MOVE

I‐MOVE, represented schematically in Figure 1, is a performance test that assesses the patient's ability to perform a sequence of 6 basic tasks: rolling over in bed, sitting up, standing, transferring to a chair, walking in the room, and walking in the hallway. Most motor functions can be assumed to be hierarchical in nature; any patient who can perform at the highest level, such as walking safely, also would be expected to perform at the lowest level.

Figure 1

Instructions for administering I‐MOVE are as follows:

• 1

  Review current orders. Exclude patients ordered on bed rest or non‐weight‐bearing or other orders precluding any of the 6 requested actions.

• 2

  Prepare environment.
• a

  Chair at bedside.

• b

  Lower side bed rail closest to chair.

• c

  Clear path for patient to ambulate.

• d

  Ensure patient dons slippers.

• e

  Flatten bed.

• f

  Ensure any gait assistive device, if generally used by the patient, is within reach from the bedside.

• 3

  Requests for patient action (for steps c through f, make available and within reach any appropriate gait‐assistance device such as walker or cane, if such is customarily used at home or newly prescribed):
• a

  With patient lying supine in bed, with close supervision, ask patient to turn from side to side in bed (request when both bed rails are up).

• b

  Lower side rail closer to chair and ask the patient to rise up to a sitting position and turn to sit up with legs dangling off the bed.

• c

  Ask the patient to stand.

• d

  Ask the patient to take a seat in the chair next to the bed.

• e

  Ask the patient to ambulate in the room.

• f

  Ask the patient to ambulate in the hallway.

• 4

  At any point if the patient seems incapable, unsteady, or unsafe to accomplish the requested task, render hands‐on assistance and immediately end the test.

• 5

  Document, by number (1‐12), the activity level successfully accomplished independently by the patient (even number levels) or accomplished with assistance (odd number levels).

• 6

  Patient may be considered independent if able to perform the activity with a normal assistive device (cane, walker, brace, or crutches) but not using furniture.

• 7

  Assistance is defined as any physical contact with the patient.

Findings

Face Validity

We sent surveys to 6 experienced practicing clinicians at our hospital: a geriatrician, a physiatrist, an exercise physiologist, an occupational therapist, a physical therapist, and a registered nurse. We asked each clinician to rate the 6 I‐MOVE elements (requested actions) for clinical relevance to mobility independence. Relevance of each element was measured on an ordinal scale with scores ranging from 1 to 4, with: 1 not relevant; 2 somewhat relevant; 3 quite relevant; and 4 very relevant. From the 5 responses we received, 4 evaluators ranked all 6 I‐MOVE requested actions as very relevant. The fifth evaluator ranked 5 of the 6 actions as very relevant and 1 action (walking in the room) as quite relevant. These results demonstrate general agreement that I‐MOVE is, at face value, a reasonable measure of independent mobility.

Interrater Reliability

The protocol was approved by the hospital's institutional review board. On a general medical unita non‐electrocardiographic telemetry, nonsurgical unit of an acute care hospital, where patients are assigned the primary service of an internal medicine physicianwe instructed 2 registered nurse (RN) volunteers (RN1 and RN2) in the I‐MOVE protocol. Each RN administered I‐MOVE independently to 41 consecutive, cognitively intact patients in a blinded fashion (ie, neither nurse was aware of the other's scoring of each patient) and within 1 hour of each other's assessment.

After administering I‐MOVE to each patient, the nurse judged and scored the patient's performance using the 12‐level I‐MOVE ordinal scale, ranging from a low value of 1, complete dependence, to the highest value of 12, complete independence. The patients' I‐MOVE score pairs recorded by RN1 and RN2 were statistically compared. Interrater reliability, a comparison of the 41 patients' score pairs, is graphically represented in Figure 2. The calculated intraclass correlation coefficient (r) was 0.90, indicating excellent agreement (r > 0.75).

Figure 2

Discussion

Traditional physical examinations by physicians and assessments by nurses do not routinely extend to standardized mobility testing and may fail to recognize disability. Of the existing mobility assessment tools, we believe that most are not suited to patients hospitalized on general medical units. I‐MOVE has been designed to address this need, with an emphasis on practicality and brevity to allow repetition at appropriate intervals (tracking), as is done for vital signs. In this initial study, I‐MOVE was found to have face‐valid content and excellent interrater agreement.

Our study had several limitations. Only 1 pair of test administrators was involved; the sample population was chosen by convenience; clustering of outcomes occurred at level 12, which may have augmented the agreement; and the study was limited to cognitively intact patients. Note that we chose to use the intraclass correlation coefficient rather than the statistic because the weighting between the ordinal I‐MOVE scores has not yet been studied and defined. Also, the weighted is asymptotically equivalent to the intraclass correlation coefficient.

I‐MOVE is intended to aid caregivers in the recognition of debility so that appropriate interventions such as physical therapy may be prescribed. It was designed to complement, not replace, specialized evaluations such as those performed by physical therapists, occupational therapists, or comprehensive geriatric assessments. This practical assessment of basic functioning may enhance communication among caregivers, patients, and patients' family members, especially with regard to discharge planning. Further study is needed to validate I‐MOVE against existing tools, evaluate I‐MOVE's utility as a vital sign, and discern whether a sharp or unexpected decline portends a medical complication.