Mitchell Levy, MD

CASE: Refractory depression

Ms. W, age 38, is brought to the emergency department after her son finds her unresponsive and calls 911. Suffering from worsening depression, she wrote a note telling her children goodbye, and overdosed on zolpidem from an old prescription and her daughter’s opioids. After being evaluated and medically cleared in the emergency department, Ms. W was admitted to the psychiatric unit.

Ms. W has a history of recurrent major depressive disorder that developed after she was sexually abused by a relative as a teen. She also has bulimia nervosa, alcohol dependence, and posttraumatic stress disorder. She was hospitalized twice for depression and suicidality but had not previously attempted suicide. In the mid-to-late 1990s, she had trials of paroxetine, clomipramine, lithium, and bupropion.

She was seen regularly in our outpatient psychiatry clinic for medication management and supportive psychotherapy. Since being followed in our clinic starting in early 2005, she has had the following medication trials:

• fluoxetine, citalopram, venlafaxine XR, and duloxetine for depression
• atomoxetine, buspirone, liothyronine, risperidone, and aripiprazole for antidepressant augmentation
• lorazepam, clonazepam, and gabapentin for anxiety
• zolpidem and trazodone for insomnia
• nortriptyline for migraine headache prophylaxis.

Some medications were not tolerated, primarily because of increased anxiety. Those that were tolerated were adequate trials in terms of dose titration and length. High-dose fluoxetine (80 mg/d) augmented by risperidone (0.375 to 0.5 mg/d) produced the most reliable and significant improvement.

Ms. W had 2 courses of electroconvulsive therapy (ECT) totaling 30 treatments—most recently in 2007—that resulted in significant memory loss with limited benefit. Premenstrual worsening of depression and suicidality were noted. In collaboration with her gynecologist, Ms. W was treated with a 3-month trial of leuprolide to suppress her ovarian axis, which was helpful. In 2008 she underwent bilateral oophorectomy. She has not had symptoms of mood elevation or psychosis. Family history includes schizophrenia, depression, anxiety, and alcoholism.

In the months before hospitalization, Ms. W had been increasingly depressed and intermittently suicidal, although she did not endorse a specific plan or intention to harm herself because she was concerned about the impact suicide would have on her children. Weight gain with risperidone had reactivated body image issues, so Ms. W stopped taking this medication 2 weeks before hospitalization. Her depression became worse, and she began using her husband’s hydrocodone/acetaminophen prescription.

The authors’ observations

Approximately 40% of patients with major depression fail to respond to an initial antidepressant trial.¹ An additional 50% of these patients will be treatment-resistant to a subsequent antidepressant.¹ Patients may be progressively less likely to respond to additional medication trials.²

One of the most rapid-acting and effective treatments for unipolar and bipolar depression is sleep deprivation. Wirz-Justice et al³ found total or partial sleep deprivation during the second half of the night induced rapid depression remission. Response rates range from 40% to 60% over hours to days.⁴ Sleep deprivation also can reduce suicidality in patients with seasonal depression.⁵ This treatment has not been widely employed, however, because up to 80% of patients who undergo sleep deprivation experience rapid and significant depressive relapse.⁴

Sleep deprivation usually is well tolerated. Potential side effects include:

• headache
• gastrointestinal upset
• fatigue
• cognitive impairment.

Less often, patients report worsening of depressive symptoms and, rarely, suicidal ideation or psychosis.⁴ Mania or hypomania are potential complications of sleep loss for patients with bipolar or unipolar depression. In a review, Oliwenstein⁶ suggested that rates of total sleep deprivation-induced mania are likely to be similar to or less than those reported for antidepressants. Because sleep deprivation can induce seizures, this therapy is contraindicated for patients with epilepsy or those at risk for seizures.⁴

Researchers have successfully explored strategies to reduce the rate of depressive relapse after sleep deprivation, including coadministering light therapy, antidepressants, lithium (particularly for bipolar depression), and sleep-phase advance.⁴ Sleep-phase advance involves shifting the sleep-wake schedule to a very early sleep time and wake-up time (such as 5 PM to midnight) for 1 day, and then pushing back this schedule by 1 or 2 hours each day until the patient is returned to a “normal” sleep schedule (such as 10 PM to 5 AM). Researchers have demonstrated that sleep-phase advance can have antidepressant effects.⁷

TREATMENT: Sleep manipulation

Ms. W is continued on fluoxetine, 80 mg/d. We opt for a trial of partial sleep deprivation and sleep-phase advance for Ms. W because of the severity of her depression, her multiple ineffective or poorly tolerated medication trials, and limited benefit from ECT. This treatment involves instituting partial sleep deprivation the first night and subsequently advancing her sleep phase over the next several days (Table 1).

Although she is sleepy the morning after partial sleep deprivation, Ms. W reports a marked improvement in her mood, decline in hopelessness, and absence of suicidal ideation. She continues the sleep-phase advance protocol for the next 3 nights and participates in cognitive-behavioral therapy groups and ward activities. Psychiatric unit staff support her continued wakefulness during sleep manipulation. Because Ms. W had previously responded to antidepressant augmentation with an atypical antipsychotic we add aripiprazole and titrate the dosage to 7.5 mg/d. We also continue fluoxetine, 80 mg/d, and add trazodone, 100 mg at bedtime, and hydroxyzine, 25 mg as needed.

Table 1

Ms. W’s chronotherapy protocol: Hours permitted for sleep*

The authors’ observations

Chronotherapy incorporates manipulations of the sleep/wake cycle such as sleep deprivation and dark or light therapy. It may use combinations of interventions to generate and sustain a response in patients with depression. In a 4-week pilot study, Moscovici et al⁸ employed a regimen of late partial sleep deprivation, light, and sleep-phase advance to generate and maintain an anti depressant response in 12 patients. Benedetti et al⁹ used a similar regimen plus lithium to successfully treat bipolar depression and sleep-phase advance to continue that response in 50% of patients for 3 months.

Circadian rhythms affect the function of serotonin (5-HT), norepinephrine, and dopamine.^9,10 In a manner similar to antidepressant medications, sleep deprivation may up-regulate or otherwise alter these neurotransmitters’ function. In animals, sleep deprivation increases serotonin function.¹¹ Several hypothetical mechanisms of action for sleep deprivation and other types of chronotherapies have been suggested (Table 2).^11-14

Chronotherapies may affect function in brain pathways, as demonstrated by neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Depression has been associated with increased or decreased brain activity measured by PET or fMRI in regions of the limbic cortex (cingulate and anterior cingulate) and frontal cortex.¹²

Wu et al¹³ examined patients treated for depression with medication and total sleep deprivation therapy. Response to treatment was associated with increased function in the cingulate, anterior cingulate, and medial prefrontal cortex as measured by PET. In contrast, mood improvement was associated with reduced baseline activity in the left medial prefrontal cortex, left frontal pole, and right lateral prefrontal cortex.

Researchers have noted the convergence of sleep-wake rhythms and abnormalities seen in depression and the subsequent link with improved sleep-wake cycles related to depression remission. Bunney and Potkin¹⁴ note the powerful effect of zeitgebers—environmental agents that reset the body’s internal clock. They suggested that sleep deprivation may affect the function of “master clock” genes involved in controlling the biological clock. These effects on the suprachiasmatic nucleus hypothalamic pacemaker may improve mood by altering control of genetic expression through chromatin remodeling of this master clock circuit.

Certain factors may increase the likelihood that a patient may respond to chronotherapy (Table 3).^9,15-17

Table 2

Sleep deprivation for depression: Possible mechanisms

Table 3

Factors that suggest a patient might respond to chronotherapy

OUTCOME: Lasting improvement

Ms. W’s mood improvement is sustained during her week-long hospitalization. At discharge she is hopeful about the future and does not have thoughts of suicide.

At subsequent outpatient visits up to 4 months after discharge, her depressive symptoms remain improved. Patient Health Questionnaire scores indicate mild depression, but Ms. W is not suicidal. She maintains a sleep schedule of 10 PM to 6:30 AM and undergoes 10,000 lux bright light therapy, which she began shortly after discharge, for 30 minutes every morning. She works more productively in psychotherapy, focusing on her eating disorder and anxiety.

Related resource

• Wu JC, Kelsoe JR, Schachat C, et al. Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biol Psychiatry. 2009; 66(3): 298-301.

Drug brand names

• Aripiprazole • Abilify
• Atomoxetine • Strattera
• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Klonopin
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Hydrocodone/APAP • Vicodin
• Hydroxyzine • Atarax, Vistaril
• Leuprolide • Lupron
• Liothyronine • Cytomel
• Lithium • Eskalith, Lithobid
• Lorazepam • Ativan
• Nortriptyline • Aventyl
• Paroxetine • Paxil
• Risperidone • Risperdal, Risperdal Consta
• Trazodone • Desyrel
• Venlafaxine XR • Effexor XR
• Zolpidem • Ambien

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Refractory depression

Ms. W, age 38, is brought to the emergency department after her son finds her unresponsive and calls 911. Suffering from worsening depression, she wrote a note telling her children goodbye, and overdosed on zolpidem from an old prescription and her daughter’s opioids. After being evaluated and medically cleared in the emergency department, Ms. W was admitted to the psychiatric unit.

Ms. W has a history of recurrent major depressive disorder that developed after she was sexually abused by a relative as a teen. She also has bulimia nervosa, alcohol dependence, and posttraumatic stress disorder. She was hospitalized twice for depression and suicidality but had not previously attempted suicide. In the mid-to-late 1990s, she had trials of paroxetine, clomipramine, lithium, and bupropion.

She was seen regularly in our outpatient psychiatry clinic for medication management and supportive psychotherapy. Since being followed in our clinic starting in early 2005, she has had the following medication trials:

• fluoxetine, citalopram, venlafaxine XR, and duloxetine for depression
• atomoxetine, buspirone, liothyronine, risperidone, and aripiprazole for antidepressant augmentation
• lorazepam, clonazepam, and gabapentin for anxiety
• zolpidem and trazodone for insomnia
• nortriptyline for migraine headache prophylaxis.

Some medications were not tolerated, primarily because of increased anxiety. Those that were tolerated were adequate trials in terms of dose titration and length. High-dose fluoxetine (80 mg/d) augmented by risperidone (0.375 to 0.5 mg/d) produced the most reliable and significant improvement.

Ms. W had 2 courses of electroconvulsive therapy (ECT) totaling 30 treatments—most recently in 2007—that resulted in significant memory loss with limited benefit. Premenstrual worsening of depression and suicidality were noted. In collaboration with her gynecologist, Ms. W was treated with a 3-month trial of leuprolide to suppress her ovarian axis, which was helpful. In 2008 she underwent bilateral oophorectomy. She has not had symptoms of mood elevation or psychosis. Family history includes schizophrenia, depression, anxiety, and alcoholism.

In the months before hospitalization, Ms. W had been increasingly depressed and intermittently suicidal, although she did not endorse a specific plan or intention to harm herself because she was concerned about the impact suicide would have on her children. Weight gain with risperidone had reactivated body image issues, so Ms. W stopped taking this medication 2 weeks before hospitalization. Her depression became worse, and she began using her husband’s hydrocodone/acetaminophen prescription.

The authors’ observations

Approximately 40% of patients with major depression fail to respond to an initial antidepressant trial.¹ An additional 50% of these patients will be treatment-resistant to a subsequent antidepressant.¹ Patients may be progressively less likely to respond to additional medication trials.²

One of the most rapid-acting and effective treatments for unipolar and bipolar depression is sleep deprivation. Wirz-Justice et al³ found total or partial sleep deprivation during the second half of the night induced rapid depression remission. Response rates range from 40% to 60% over hours to days.⁴ Sleep deprivation also can reduce suicidality in patients with seasonal depression.⁵ This treatment has not been widely employed, however, because up to 80% of patients who undergo sleep deprivation experience rapid and significant depressive relapse.⁴

Sleep deprivation usually is well tolerated. Potential side effects include:

• headache
• gastrointestinal upset
• fatigue
• cognitive impairment.

Less often, patients report worsening of depressive symptoms and, rarely, suicidal ideation or psychosis.⁴ Mania or hypomania are potential complications of sleep loss for patients with bipolar or unipolar depression. In a review, Oliwenstein⁶ suggested that rates of total sleep deprivation-induced mania are likely to be similar to or less than those reported for antidepressants. Because sleep deprivation can induce seizures, this therapy is contraindicated for patients with epilepsy or those at risk for seizures.⁴

Researchers have successfully explored strategies to reduce the rate of depressive relapse after sleep deprivation, including coadministering light therapy, antidepressants, lithium (particularly for bipolar depression), and sleep-phase advance.⁴ Sleep-phase advance involves shifting the sleep-wake schedule to a very early sleep time and wake-up time (such as 5 PM to midnight) for 1 day, and then pushing back this schedule by 1 or 2 hours each day until the patient is returned to a “normal” sleep schedule (such as 10 PM to 5 AM). Researchers have demonstrated that sleep-phase advance can have antidepressant effects.⁷

TREATMENT: Sleep manipulation

Ms. W is continued on fluoxetine, 80 mg/d. We opt for a trial of partial sleep deprivation and sleep-phase advance for Ms. W because of the severity of her depression, her multiple ineffective or poorly tolerated medication trials, and limited benefit from ECT. This treatment involves instituting partial sleep deprivation the first night and subsequently advancing her sleep phase over the next several days (Table 1).

Although she is sleepy the morning after partial sleep deprivation, Ms. W reports a marked improvement in her mood, decline in hopelessness, and absence of suicidal ideation. She continues the sleep-phase advance protocol for the next 3 nights and participates in cognitive-behavioral therapy groups and ward activities. Psychiatric unit staff support her continued wakefulness during sleep manipulation. Because Ms. W had previously responded to antidepressant augmentation with an atypical antipsychotic we add aripiprazole and titrate the dosage to 7.5 mg/d. We also continue fluoxetine, 80 mg/d, and add trazodone, 100 mg at bedtime, and hydroxyzine, 25 mg as needed.

Table 1

Ms. W’s chronotherapy protocol: Hours permitted for sleep*

The authors’ observations

Chronotherapy incorporates manipulations of the sleep/wake cycle such as sleep deprivation and dark or light therapy. It may use combinations of interventions to generate and sustain a response in patients with depression. In a 4-week pilot study, Moscovici et al⁸ employed a regimen of late partial sleep deprivation, light, and sleep-phase advance to generate and maintain an anti depressant response in 12 patients. Benedetti et al⁹ used a similar regimen plus lithium to successfully treat bipolar depression and sleep-phase advance to continue that response in 50% of patients for 3 months.

Circadian rhythms affect the function of serotonin (5-HT), norepinephrine, and dopamine.^9,10 In a manner similar to antidepressant medications, sleep deprivation may up-regulate or otherwise alter these neurotransmitters’ function. In animals, sleep deprivation increases serotonin function.¹¹ Several hypothetical mechanisms of action for sleep deprivation and other types of chronotherapies have been suggested (Table 2).^11-14

Chronotherapies may affect function in brain pathways, as demonstrated by neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Depression has been associated with increased or decreased brain activity measured by PET or fMRI in regions of the limbic cortex (cingulate and anterior cingulate) and frontal cortex.¹²

Wu et al¹³ examined patients treated for depression with medication and total sleep deprivation therapy. Response to treatment was associated with increased function in the cingulate, anterior cingulate, and medial prefrontal cortex as measured by PET. In contrast, mood improvement was associated with reduced baseline activity in the left medial prefrontal cortex, left frontal pole, and right lateral prefrontal cortex.

Researchers have noted the convergence of sleep-wake rhythms and abnormalities seen in depression and the subsequent link with improved sleep-wake cycles related to depression remission. Bunney and Potkin¹⁴ note the powerful effect of zeitgebers—environmental agents that reset the body’s internal clock. They suggested that sleep deprivation may affect the function of “master clock” genes involved in controlling the biological clock. These effects on the suprachiasmatic nucleus hypothalamic pacemaker may improve mood by altering control of genetic expression through chromatin remodeling of this master clock circuit.

Certain factors may increase the likelihood that a patient may respond to chronotherapy (Table 3).^9,15-17

Table 2

Sleep deprivation for depression: Possible mechanisms

Table 3

Factors that suggest a patient might respond to chronotherapy

OUTCOME: Lasting improvement

Ms. W’s mood improvement is sustained during her week-long hospitalization. At discharge she is hopeful about the future and does not have thoughts of suicide.

At subsequent outpatient visits up to 4 months after discharge, her depressive symptoms remain improved. Patient Health Questionnaire scores indicate mild depression, but Ms. W is not suicidal. She maintains a sleep schedule of 10 PM to 6:30 AM and undergoes 10,000 lux bright light therapy, which she began shortly after discharge, for 30 minutes every morning. She works more productively in psychotherapy, focusing on her eating disorder and anxiety.

Related resource

• Wu JC, Kelsoe JR, Schachat C, et al. Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biol Psychiatry. 2009; 66(3): 298-301.

Drug brand names

• Aripiprazole • Abilify
• Atomoxetine • Strattera
• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Klonopin
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Hydrocodone/APAP • Vicodin
• Hydroxyzine • Atarax, Vistaril
• Leuprolide • Lupron
• Liothyronine • Cytomel
• Lithium • Eskalith, Lithobid
• Lorazepam • Ativan
• Nortriptyline • Aventyl
• Paroxetine • Paxil
• Risperidone • Risperdal, Risperdal Consta
• Trazodone • Desyrel
• Venlafaxine XR • Effexor XR
• Zolpidem • Ambien

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Refractory depression

Ms. W, age 38, is brought to the emergency department after her son finds her unresponsive and calls 911. Suffering from worsening depression, she wrote a note telling her children goodbye, and overdosed on zolpidem from an old prescription and her daughter’s opioids. After being evaluated and medically cleared in the emergency department, Ms. W was admitted to the psychiatric unit.

Ms. W has a history of recurrent major depressive disorder that developed after she was sexually abused by a relative as a teen. She also has bulimia nervosa, alcohol dependence, and posttraumatic stress disorder. She was hospitalized twice for depression and suicidality but had not previously attempted suicide. In the mid-to-late 1990s, she had trials of paroxetine, clomipramine, lithium, and bupropion.

She was seen regularly in our outpatient psychiatry clinic for medication management and supportive psychotherapy. Since being followed in our clinic starting in early 2005, she has had the following medication trials:

• fluoxetine, citalopram, venlafaxine XR, and duloxetine for depression
• atomoxetine, buspirone, liothyronine, risperidone, and aripiprazole for antidepressant augmentation
• lorazepam, clonazepam, and gabapentin for anxiety
• zolpidem and trazodone for insomnia
• nortriptyline for migraine headache prophylaxis.

Some medications were not tolerated, primarily because of increased anxiety. Those that were tolerated were adequate trials in terms of dose titration and length. High-dose fluoxetine (80 mg/d) augmented by risperidone (0.375 to 0.5 mg/d) produced the most reliable and significant improvement.

Ms. W had 2 courses of electroconvulsive therapy (ECT) totaling 30 treatments—most recently in 2007—that resulted in significant memory loss with limited benefit. Premenstrual worsening of depression and suicidality were noted. In collaboration with her gynecologist, Ms. W was treated with a 3-month trial of leuprolide to suppress her ovarian axis, which was helpful. In 2008 she underwent bilateral oophorectomy. She has not had symptoms of mood elevation or psychosis. Family history includes schizophrenia, depression, anxiety, and alcoholism.

In the months before hospitalization, Ms. W had been increasingly depressed and intermittently suicidal, although she did not endorse a specific plan or intention to harm herself because she was concerned about the impact suicide would have on her children. Weight gain with risperidone had reactivated body image issues, so Ms. W stopped taking this medication 2 weeks before hospitalization. Her depression became worse, and she began using her husband’s hydrocodone/acetaminophen prescription.

The authors’ observations

Approximately 40% of patients with major depression fail to respond to an initial antidepressant trial.¹ An additional 50% of these patients will be treatment-resistant to a subsequent antidepressant.¹ Patients may be progressively less likely to respond to additional medication trials.²

One of the most rapid-acting and effective treatments for unipolar and bipolar depression is sleep deprivation. Wirz-Justice et al³ found total or partial sleep deprivation during the second half of the night induced rapid depression remission. Response rates range from 40% to 60% over hours to days.⁴ Sleep deprivation also can reduce suicidality in patients with seasonal depression.⁵ This treatment has not been widely employed, however, because up to 80% of patients who undergo sleep deprivation experience rapid and significant depressive relapse.⁴

Sleep deprivation usually is well tolerated. Potential side effects include:

• headache
• gastrointestinal upset
• fatigue
• cognitive impairment.

Less often, patients report worsening of depressive symptoms and, rarely, suicidal ideation or psychosis.⁴ Mania or hypomania are potential complications of sleep loss for patients with bipolar or unipolar depression. In a review, Oliwenstein⁶ suggested that rates of total sleep deprivation-induced mania are likely to be similar to or less than those reported for antidepressants. Because sleep deprivation can induce seizures, this therapy is contraindicated for patients with epilepsy or those at risk for seizures.⁴

Researchers have successfully explored strategies to reduce the rate of depressive relapse after sleep deprivation, including coadministering light therapy, antidepressants, lithium (particularly for bipolar depression), and sleep-phase advance.⁴ Sleep-phase advance involves shifting the sleep-wake schedule to a very early sleep time and wake-up time (such as 5 PM to midnight) for 1 day, and then pushing back this schedule by 1 or 2 hours each day until the patient is returned to a “normal” sleep schedule (such as 10 PM to 5 AM). Researchers have demonstrated that sleep-phase advance can have antidepressant effects.⁷

TREATMENT: Sleep manipulation

Ms. W is continued on fluoxetine, 80 mg/d. We opt for a trial of partial sleep deprivation and sleep-phase advance for Ms. W because of the severity of her depression, her multiple ineffective or poorly tolerated medication trials, and limited benefit from ECT. This treatment involves instituting partial sleep deprivation the first night and subsequently advancing her sleep phase over the next several days (Table 1).

Although she is sleepy the morning after partial sleep deprivation, Ms. W reports a marked improvement in her mood, decline in hopelessness, and absence of suicidal ideation. She continues the sleep-phase advance protocol for the next 3 nights and participates in cognitive-behavioral therapy groups and ward activities. Psychiatric unit staff support her continued wakefulness during sleep manipulation. Because Ms. W had previously responded to antidepressant augmentation with an atypical antipsychotic we add aripiprazole and titrate the dosage to 7.5 mg/d. We also continue fluoxetine, 80 mg/d, and add trazodone, 100 mg at bedtime, and hydroxyzine, 25 mg as needed.

Table 1

Ms. W’s chronotherapy protocol: Hours permitted for sleep*

The authors’ observations

Chronotherapy incorporates manipulations of the sleep/wake cycle such as sleep deprivation and dark or light therapy. It may use combinations of interventions to generate and sustain a response in patients with depression. In a 4-week pilot study, Moscovici et al⁸ employed a regimen of late partial sleep deprivation, light, and sleep-phase advance to generate and maintain an anti depressant response in 12 patients. Benedetti et al⁹ used a similar regimen plus lithium to successfully treat bipolar depression and sleep-phase advance to continue that response in 50% of patients for 3 months.

Circadian rhythms affect the function of serotonin (5-HT), norepinephrine, and dopamine.^9,10 In a manner similar to antidepressant medications, sleep deprivation may up-regulate or otherwise alter these neurotransmitters’ function. In animals, sleep deprivation increases serotonin function.¹¹ Several hypothetical mechanisms of action for sleep deprivation and other types of chronotherapies have been suggested (Table 2).^11-14

Chronotherapies may affect function in brain pathways, as demonstrated by neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Depression has been associated with increased or decreased brain activity measured by PET or fMRI in regions of the limbic cortex (cingulate and anterior cingulate) and frontal cortex.¹²

Wu et al¹³ examined patients treated for depression with medication and total sleep deprivation therapy. Response to treatment was associated with increased function in the cingulate, anterior cingulate, and medial prefrontal cortex as measured by PET. In contrast, mood improvement was associated with reduced baseline activity in the left medial prefrontal cortex, left frontal pole, and right lateral prefrontal cortex.

Researchers have noted the convergence of sleep-wake rhythms and abnormalities seen in depression and the subsequent link with improved sleep-wake cycles related to depression remission. Bunney and Potkin¹⁴ note the powerful effect of zeitgebers—environmental agents that reset the body’s internal clock. They suggested that sleep deprivation may affect the function of “master clock” genes involved in controlling the biological clock. These effects on the suprachiasmatic nucleus hypothalamic pacemaker may improve mood by altering control of genetic expression through chromatin remodeling of this master clock circuit.

Certain factors may increase the likelihood that a patient may respond to chronotherapy (Table 3).^9,15-17

Table 2

Sleep deprivation for depression: Possible mechanisms

Table 3

Factors that suggest a patient might respond to chronotherapy

OUTCOME: Lasting improvement

Ms. W’s mood improvement is sustained during her week-long hospitalization. At discharge she is hopeful about the future and does not have thoughts of suicide.

At subsequent outpatient visits up to 4 months after discharge, her depressive symptoms remain improved. Patient Health Questionnaire scores indicate mild depression, but Ms. W is not suicidal. She maintains a sleep schedule of 10 PM to 6:30 AM and undergoes 10,000 lux bright light therapy, which she began shortly after discharge, for 30 minutes every morning. She works more productively in psychotherapy, focusing on her eating disorder and anxiety.

Related resource

• Wu JC, Kelsoe JR, Schachat C, et al. Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biol Psychiatry. 2009; 66(3): 298-301.

Drug brand names

• Aripiprazole • Abilify
• Atomoxetine • Strattera
• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Klonopin
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Hydrocodone/APAP • Vicodin
• Hydroxyzine • Atarax, Vistaril
• Leuprolide • Lupron
• Liothyronine • Cytomel
• Lithium • Eskalith, Lithobid
• Lorazepam • Ativan
• Nortriptyline • Aventyl
• Paroxetine • Paxil
• Risperidone • Risperdal, Risperdal Consta
• Trazodone • Desyrel
• Venlafaxine XR • Effexor XR
• Zolpidem • Ambien

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

The incidence of severe sepsis (sepsis with organ dysfunction) is increasing.1 The initial diagnosis and management of severe sepsis may occur in the ED, the ICU, or the hospital ward.

Several recently published studies have demonstrated decreased mortality and morbidity as a result of interventions and therapeutics applied to patients with sepsis.2-5 These new data, resulting from rigorously performed, randomized controlled trials, combined with previous data for beneficial interventions not specific to sepsis management (such as DVT and stress ulcer prophylaxis) and consensus opinion where no evidence exists lend significant weight to the belief that critical care clinicians can now significantly reduce mortality in patients with severe sepsis and septic shock.6-9

Protocolized care now exists for heart attack and stroke, which is based on recent advances as demonstrated by the medical literature. Until now there has been no attempt to reproduce such an approach in severe sepsis. The Surviving Sepsis Campaign hopes to change that.

The Surviving Sepsis Campaign is administered by the Society of Critical Care Medicine (SCCM), the European Society of Intensive Care Medicine (ESICM), and the International Sepsis Forum (ISF) and is open to all industry for funding through unrestricted educational grants. Contributors to date include Baxter, Edwards, and Eli Lilly.

The first phase was the introduction of the campaign at several major international critical care medicine conferences, the ESICM meeting in Barcelona in 2002, and the SCCM meeting in 2003. The stated goal of the campaign is to decrease the mortality from severe sepsis by 25% in five years.

Phase 2 of the campaign was aimed at producing guidelines for the management of sepsis. In 2003, critical care and infectious disease experts representing 11 international organizations developed evidence-based management guidelines for severe sepsis and septic shock for practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign.

Pediatric considerations were provided to contrast adult and pediatric management. The resulting recommendations represent an attempt to facilitate a rapid change in the standard of care for management of sepsis, based on the quality of available published data and expert opinion where no literature guidance is available. The guidelines manuscript was published in both Critical Care Medicine and Intensive Care Medicine.10,11 The publication of this manuscript represents an historic step for critical care worldwide. These guidelines represent an international consensus on the best available standard for management of sepsis.

Key Recommendations

Key recommendations (listed by category and not by hierarchy) include:

• Early goal-directed resuscitation of the septic patient during the first six hours after recognition;
• Appropriate diagnostic studies to ascertain causative organisms before starting antibiotics;
• Early administration of broad-spectrum antibiotic therapy;
• Reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate;
• A usual seven to 10 days of antibiotic therapy guided by clinical response;
• Source control with attention to the method that balances risks and benefits;
• Equivalence of crystalloid and colloid resuscitation;
• Aggressive fluid challenge to restore mean circulating filling pressure;
• Vasopressor preference for norepinephrine and dopamine;
• Cautious use of vasopressin pending further studies;
• Avoidance of low-dose dopamine administration for renal protection;
• Consideration of dobutamine inotropic therapy in some clinical situations;
• Avoidance of supranormal oxygen delivery as a goal of therapy;
• Stress-dose steroid therapy for septic shock;
• Use of recombinant activated protein C in patients with severe sepsis and high risk for death;
• Resolution of tissue hypoperfusion and targeting a hemoglobin of 7-9 g/dL in the absence of coronary artery disease or acute hemorrhage;
• Appropriate use of fresh frozen plasma and platelets;
• A low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome;
• Application of a minimal amount of positive end expiratory pressure in acute lung injury/acute respiratory distress syndrome;
• A semi-recumbent bed position unless contraindicated;
• Protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening;
• Avoidance of neuromuscular blockers, if at all possible;
• Maintenance of blood glucose <150 mg/dL after initial stabilization;
• Equivalence of continuous veno-veno hemofiltration (CVVH) and intermittent hemodialysis;
• Lack of utility of bicarbonate use for pH 7.15 or greater;
• Use of DVT/stress ulcer prophylaxis; and
• Consideration of limitation of support where appropriate.

Pediatric considerations include a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40-60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic endpoints; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control.

Operationalizing the Guidelines

Unfortunately, clinicians change slowly. Historically, transfer of research from the bench to the bedside is a long, tortuous process—one that is not driven by anything clear and that seems to be based more on fad and coincidence than on a keen, evidence-based evaluation of the literature. Phase 3 of the campaign hopes to change that.

Phase 3 of the campaign (www.survivingsepsis.org) aims to operationalize the guidelines to create a global standard of care for sepsis management.12 The guidelines will be transformed into user-friendly tools that allow clinicians to easily incorporate these new recommendations into bedside care. The first step in this next phase has been a joint effort with the Institute of Healthcare Improvement (IHI) to deploy a “change bundle” based on a core set of the previous recommendations into the IHI’s collaborative system. Chart review or concurrent data gathering will identify and track changes in practice and clinical outcomes. Engendering evidence-based change through motivational strategies while monitoring and sharing the results with healthcare practitioners is the key to improving outcomes in severe sepsis.

The severe sepsis bundles form the core of the Surviving Sepsis Campaign. A “bundle” is a group of interventions related to a disease process. When executed together, the interventions produce better outcomes than when implemented individually. The individual bundle elements are built on evidence-based practices. The science behind the elements of a bundle is so well established that their implementation should be considered a generally accepted practice. Develop a bundle process in the following way:

1. Identify a set of four to six evidence-based interventions that apply to a cohort of patients with a common disease or a common location. An example might be patients with sepsis admitted to the ICU;
2. Develop the will in the providers to deliver the interventions every time they are indicated;
3. Redesign the delivery system to ensure the interventions in the bundle are delivered; and
4. Measure related outcomes to ascertain the effects of the changes in the delivery system.

The sepsis bundles were developed in just such a manner, based on the experience of the ventilator bundle. The goal now is to motivate providers to deliver the sepsis interventions every time they are indicated and measure them in an all-or-nothing way. We believe that if the bundle elements are reliably performed we can achieve the desired outcome of reducing sepsis-related deaths by 25%.

These elements distill the Surviving Sepsis Campaign practice guidelines into a manageable format for use at most institutions. The bundles represent the specific changes the campaign has identified as essential to the care of severely septic patients. Following the severe sepsis bundles will eliminate the piecemeal or inappropriate application of standards for sepsis care that characterize most clinical environments today.

Hospitals should implement two different severe sepsis bundles. Each bundle articulates objectives to be accomplished within specific time frames.

Sepsis Resuscitation Bundle

The severe sepsis resuscitation bundle describes seven tasks that should begin immediately but must be accomplished within the first six hours of presentation for patients with severe sepsis or septic shock. Some items may not be completed if the clinical conditions described in the bundle do not prevail in a particular case, but clinicians must assess for them. The goal is to perform all indicated tasks 100% of the time within the first six hours of identification of severe sepsis. The tasks are:

1. Measure serum lactate;
2. Obtain blood cultures prior to antibiotic administration;
3. Administer broad-spectrum antibiotics within three hours from time of presentation for ED admissions and one hour for non-ED ICU admissions;
4. In the event of hypotension and/or lactate >4 mmol/L (36 mg/dL):

   1. Deliver an initial minimum of 20 ml/kg of crystalloid (or colloid equivalent); and
   2. Apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) ≥65 mm Hg;

5. In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/L (36 mg/dL):

   1. Achieve central venous pressure (CVP) of ≥8-12 mm Hg; and
   2. Achieve central venous oxygen saturation (ScvO2) of Surviving Sepsis Campaign70%. (Achieving a mixed venous oxygen saturation (SvO2) of 65% is an acceptable alternative.)

Sepsis Management Bundle

The severe sepsis management bundle lists four management goals. Efforts to accomplish these tasks should also begin immediately, but these items may be completed within 24 hours of presentation for patients with severe sepsis or septic shock.

1. Administer low-dose steroids for septic shock in accordance with a standardized ICU policy;
2. Administer drotrecogin alfa (activated) in accordance with a standardized ICU policy;
3. Maintain glucose control ≥ lower limit of normal, but <150 mg/dL (8.3 mmol/L); and
4. Maintain inspiratory plateau pressures <30 cm H2O for mechanically ventilated patients.

click for large version

Team Effort

To achieve the goal of reducing mortality by 25% by 2008, everyone involved with the care of severe sepsis patients must be included, work processes must be carefully scripted and standardized, and commitment to this effort must be elevated. This must be a team effort that crosses disciplines and departments; it requires leadership, support from the entire organization, and buy-in from all stakeholders involved with the care of these patients.

Three levels of participation exist in creating successful change:

1) Active working teams are responsible for daily planning, documentation, communication, education, monitoring, and evaluation of activities. The working team must have representation from all departments involved in the change processes ICU, ED, pulmonary department, pharmacy, etc. The team should also be multidisciplinary, comprising physicians, nurses, pharmacists, respiratory therapists, and other staff with roles in the specific change process, such as clerks and technicians. Team members should be knowledgeable about the specific aims, the current local work processes, the associated literature, and any environmental issues that will be affected by these changes.

2) A leadership group or person within the team helps remove barriers, provides resources, monitors global progress, and gives suggestions from an institutional perspective. The working team needs someone with authority in the organization to overcome barriers and to allocate the time and resources the team needs to achieve its aim. Leadership needs to understand how the proposed changes will affect various parts of the system and the more remote consequences such changes might trigger.

3) Providers and stakeholders must be kept informed. Procedures are needed to keep them informed, to receive their feedback, and to ensure them that their responses are respected. This gives stakeholders a sense of ownership and facilitates implementation of the new processes.

click for large version

Protocols

Teams should use the bundles to create customized protocols and pathways that will function well within their institutions. However, all of the elements in the bundles must be incorporated into the protocols. The protocols should mirror the bundles but allow flexibility to accommodate the specific needs of a local hospital. The severe sepsis bundles (and thereby the hospital’s protocol) form the basis for the measurements the team will conduct. If all of the elements of the bundles are not incorporated into your customized protocol, your performance on the measures will suffer.

A strong protocol will accomplish all of the items listed in the severe sepsis bundles. If the protocol designer pays careful attention to the details in the bundles, the protocol will score well on the severe sepsis quality indicators. Hospitals will want to publicize their efforts with regard to improving sepsis care and make the protocol an integral part of their rollout strategy. It is imperative to launch an educational initiative regarding the effort.

Examples of sepsis screening and management protocols are available on the Surviving Sepsis Campaign IHI Web site and are rendered on this page as “Protocol A: Create a protocol and educate users” and as “Prot0col B.” The easiest way to get to that page of the IHI Web site is through the home page link from the Surviving Sepsis Campaign Web site, www.survivingsepsis.org. These highly visual and easy-to-follow pathways exemplify ways to encourage adherence to a protocol. Notice that the “Sepsis Screening Protocol” (p. 25) complies with the terms of the severe sepsis bundles. Posting these types of algorithms prominently in the ED, hospital wards, and ICU, and making them readily available in laminated and PDA format, can have a significant impact on performance improvement programs.

These flow diagrams may be incorporated into lectures and training programs to support your efforts to change care at the bedside. You can adapt the algorithms to fit the needs of your individual institution, but keep in mind the need to comply with the overall structure of the severe sepsis bundles.

click for large version

Data Collection

Data collection can seem like an onerous duty in any quality improvement project. Nevertheless, it is essential for improvement. Without attention to measurement, how will you know that your efforts are leading to improvement? At most hospitals, the magnitude of the data collection effort will not be huge as it will be relative to the number of severely septic patients cared for in the ICU.

Generally, hospitals report three to four severely septic patients are treated in one week’s time. This means that zero, one, or two severely septic patients’ charts will need to be abstracted each day in an average-size hospital. If abstraction takes between 20–30 minutes per chart, the daily time for this effort may range from 30–90 minutes daily. This relatively small burden is likely to represent an initial challenge to anyone unfamiliar with the organization of the chart and the measurement forms, or tools, used by the Surviving Sepsis Campaign for data collection. In time, however, data collection will become easier as the chart and the tools provided by the Surviving Sepsis Campaign will become more familiar. Bundle implementation and data collection have begun in hospitals throughout Europe, Latin America, the United Kingdom, and the United States.

The measurement tools were created to achieve a uniform system of data gathering, collation, and calculation across hospitals. Without the measurement tools, teams armed with only the concepts in the severe sepsis bundles would need to decide how to gather data from charts and put it in a format consistent with the calculations listed in the severe sepsis quality indicators. If any hospital were to undertake such a task on its own, it would quickly find that its results were not comparable across institutions because scores of other hospitals would have derived their results by entirely different means.

The Surviving Sepsis Campaign aims to make using the measurement tools as easy as possible for those involved in collecting data. Several basic tools organize data from the patient’s chart. Initially, a paper set of measurement tools was developed to help hospitals orchestrate data collection. Although a database now performs much of the work formerly done on paper, some use of paper tools may be helpful.

For example, the Surviving Sepsis Campaign’s screening tool for severe sepsis is integrated into the database. However, a paper version readily accessible to nurses and clinicians in the ED triage area, the medical and surgical nursing stations, and even the ICU itself will still be practical.

Likewise, some data collectors might find that first capturing on paper the data abstracted from the chart and subsequently entering it into the database is preferable. Most users are likely to find, however, that bringing the database to the ICU on a laptop and directly entering data is the easiest solution.

The most up-to-date paper versions of the tools and the Surviving Sepsis Campaign database can be found on the Institute of Healthcare Improvement Web site. The easiest way to get to that page of the Institute of Healthcare Improvement Web site is by home page linkage from the Surviving Sepsis Campaign Web site, www.survivingsepsis.org. An implementation manual is also available that will facilitate initiation of the Surviving Sepsis Campaign performance improvement program as well as installation and use of the associated electronic database.

Conclusion

The Surviving Sepsis Campaign represents an important step for international critical care societies. Recognizing the long history of delay in incorporating research into bedside care, these critical care societies have committed to working together to facilitate bench-to-bedside transfer of recent research. Thus, the campaign represents an ongoing commitment to excellence in patient care. The Surviving Sepsis Campaign has established a target of a 25% reduction in mortality worldwide from sepsis over the next five years. If the Surviving Sepsis Campaign is able to bring the guidelines into routine use, it is possible to achieve this goal. For the campaign to be successful, it will require more than good publicity. It will require a further commitment from bedside clinicians to appraise new research critically and adopt interventions proven to be effective rapidly.

Hospitalists interested in more information about instituting the Surviving Sepsis Campaign and performance improvement package in their hospital should e-mail the Surviving Sepsis Campaign user group program manager at dskbranch@mac.com. TH

References

1. Angus DC, Linde-Zwirble WT, Lidicer J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303-1310.
2. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-1377.
3. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862-871.
4. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344(10)699-709.
5. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342:1301-1308.
6. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion in critical care. N Engl J Med. 1999;340:409-4178.
7. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359-1367.
8. Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in medical patients with enoxaparin study group. N Engl J Med. 1999;341:793-800.
9. Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med. 1998;338:791-797.
10. Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-873.
11. Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004;30:536-55.
12. Levy MM, Pronovost PJ, Dellinger RP, et al. Sepsis change bundles: converting guidelines into meaningful change in behavior and clinical outcome. Crit Care Med. 2004;32(suppl):S595-S597.

The incidence of severe sepsis (sepsis with organ dysfunction) is increasing.1 The initial diagnosis and management of severe sepsis may occur in the ED, the ICU, or the hospital ward.

Several recently published studies have demonstrated decreased mortality and morbidity as a result of interventions and therapeutics applied to patients with sepsis.2-5 These new data, resulting from rigorously performed, randomized controlled trials, combined with previous data for beneficial interventions not specific to sepsis management (such as DVT and stress ulcer prophylaxis) and consensus opinion where no evidence exists lend significant weight to the belief that critical care clinicians can now significantly reduce mortality in patients with severe sepsis and septic shock.6-9

Protocolized care now exists for heart attack and stroke, which is based on recent advances as demonstrated by the medical literature. Until now there has been no attempt to reproduce such an approach in severe sepsis. The Surviving Sepsis Campaign hopes to change that.

The Surviving Sepsis Campaign is administered by the Society of Critical Care Medicine (SCCM), the European Society of Intensive Care Medicine (ESICM), and the International Sepsis Forum (ISF) and is open to all industry for funding through unrestricted educational grants. Contributors to date include Baxter, Edwards, and Eli Lilly.

The first phase was the introduction of the campaign at several major international critical care medicine conferences, the ESICM meeting in Barcelona in 2002, and the SCCM meeting in 2003. The stated goal of the campaign is to decrease the mortality from severe sepsis by 25% in five years.

Phase 2 of the campaign was aimed at producing guidelines for the management of sepsis. In 2003, critical care and infectious disease experts representing 11 international organizations developed evidence-based management guidelines for severe sepsis and septic shock for practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign.

Pediatric considerations were provided to contrast adult and pediatric management. The resulting recommendations represent an attempt to facilitate a rapid change in the standard of care for management of sepsis, based on the quality of available published data and expert opinion where no literature guidance is available. The guidelines manuscript was published in both Critical Care Medicine and Intensive Care Medicine.10,11 The publication of this manuscript represents an historic step for critical care worldwide. These guidelines represent an international consensus on the best available standard for management of sepsis.

Key Recommendations

Key recommendations (listed by category and not by hierarchy) include:

• Early goal-directed resuscitation of the septic patient during the first six hours after recognition;
• Appropriate diagnostic studies to ascertain causative organisms before starting antibiotics;
• Early administration of broad-spectrum antibiotic therapy;
• Reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate;
• A usual seven to 10 days of antibiotic therapy guided by clinical response;
• Source control with attention to the method that balances risks and benefits;
• Equivalence of crystalloid and colloid resuscitation;
• Aggressive fluid challenge to restore mean circulating filling pressure;
• Vasopressor preference for norepinephrine and dopamine;
• Cautious use of vasopressin pending further studies;
• Avoidance of low-dose dopamine administration for renal protection;
• Consideration of dobutamine inotropic therapy in some clinical situations;
• Avoidance of supranormal oxygen delivery as a goal of therapy;
• Stress-dose steroid therapy for septic shock;
• Use of recombinant activated protein C in patients with severe sepsis and high risk for death;
• Resolution of tissue hypoperfusion and targeting a hemoglobin of 7-9 g/dL in the absence of coronary artery disease or acute hemorrhage;
• Appropriate use of fresh frozen plasma and platelets;
• A low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome;
• Application of a minimal amount of positive end expiratory pressure in acute lung injury/acute respiratory distress syndrome;
• A semi-recumbent bed position unless contraindicated;
• Protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening;
• Avoidance of neuromuscular blockers, if at all possible;
• Maintenance of blood glucose <150 mg/dL after initial stabilization;
• Equivalence of continuous veno-veno hemofiltration (CVVH) and intermittent hemodialysis;
• Lack of utility of bicarbonate use for pH 7.15 or greater;
• Use of DVT/stress ulcer prophylaxis; and
• Consideration of limitation of support where appropriate.

Pediatric considerations include a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40-60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic endpoints; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control.

Operationalizing the Guidelines

Unfortunately, clinicians change slowly. Historically, transfer of research from the bench to the bedside is a long, tortuous process—one that is not driven by anything clear and that seems to be based more on fad and coincidence than on a keen, evidence-based evaluation of the literature. Phase 3 of the campaign hopes to change that.

Phase 3 of the campaign (www.survivingsepsis.org) aims to operationalize the guidelines to create a global standard of care for sepsis management.12 The guidelines will be transformed into user-friendly tools that allow clinicians to easily incorporate these new recommendations into bedside care. The first step in this next phase has been a joint effort with the Institute of Healthcare Improvement (IHI) to deploy a “change bundle” based on a core set of the previous recommendations into the IHI’s collaborative system. Chart review or concurrent data gathering will identify and track changes in practice and clinical outcomes. Engendering evidence-based change through motivational strategies while monitoring and sharing the results with healthcare practitioners is the key to improving outcomes in severe sepsis.

The severe sepsis bundles form the core of the Surviving Sepsis Campaign. A “bundle” is a group of interventions related to a disease process. When executed together, the interventions produce better outcomes than when implemented individually. The individual bundle elements are built on evidence-based practices. The science behind the elements of a bundle is so well established that their implementation should be considered a generally accepted practice. Develop a bundle process in the following way:

1. Identify a set of four to six evidence-based interventions that apply to a cohort of patients with a common disease or a common location. An example might be patients with sepsis admitted to the ICU;
2. Develop the will in the providers to deliver the interventions every time they are indicated;
3. Redesign the delivery system to ensure the interventions in the bundle are delivered; and
4. Measure related outcomes to ascertain the effects of the changes in the delivery system.

The sepsis bundles were developed in just such a manner, based on the experience of the ventilator bundle. The goal now is to motivate providers to deliver the sepsis interventions every time they are indicated and measure them in an all-or-nothing way. We believe that if the bundle elements are reliably performed we can achieve the desired outcome of reducing sepsis-related deaths by 25%.

These elements distill the Surviving Sepsis Campaign practice guidelines into a manageable format for use at most institutions. The bundles represent the specific changes the campaign has identified as essential to the care of severely septic patients. Following the severe sepsis bundles will eliminate the piecemeal or inappropriate application of standards for sepsis care that characterize most clinical environments today.

Hospitals should implement two different severe sepsis bundles. Each bundle articulates objectives to be accomplished within specific time frames.

Sepsis Resuscitation Bundle

The severe sepsis resuscitation bundle describes seven tasks that should begin immediately but must be accomplished within the first six hours of presentation for patients with severe sepsis or septic shock. Some items may not be completed if the clinical conditions described in the bundle do not prevail in a particular case, but clinicians must assess for them. The goal is to perform all indicated tasks 100% of the time within the first six hours of identification of severe sepsis. The tasks are:

1. Measure serum lactate;
2. Obtain blood cultures prior to antibiotic administration;
3. Administer broad-spectrum antibiotics within three hours from time of presentation for ED admissions and one hour for non-ED ICU admissions;
4. In the event of hypotension and/or lactate >4 mmol/L (36 mg/dL):

   1. Deliver an initial minimum of 20 ml/kg of crystalloid (or colloid equivalent); and
   2. Apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) ≥65 mm Hg;

5. In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/L (36 mg/dL):

   1. Achieve central venous pressure (CVP) of ≥8-12 mm Hg; and
   2. Achieve central venous oxygen saturation (ScvO2) of Surviving Sepsis Campaign70%. (Achieving a mixed venous oxygen saturation (SvO2) of 65% is an acceptable alternative.)

Sepsis Management Bundle

The severe sepsis management bundle lists four management goals. Efforts to accomplish these tasks should also begin immediately, but these items may be completed within 24 hours of presentation for patients with severe sepsis or septic shock.

1. Administer low-dose steroids for septic shock in accordance with a standardized ICU policy;
2. Administer drotrecogin alfa (activated) in accordance with a standardized ICU policy;
3. Maintain glucose control ≥ lower limit of normal, but <150 mg/dL (8.3 mmol/L); and
4. Maintain inspiratory plateau pressures <30 cm H2O for mechanically ventilated patients.

click for large version

Team Effort

To achieve the goal of reducing mortality by 25% by 2008, everyone involved with the care of severe sepsis patients must be included, work processes must be carefully scripted and standardized, and commitment to this effort must be elevated. This must be a team effort that crosses disciplines and departments; it requires leadership, support from the entire organization, and buy-in from all stakeholders involved with the care of these patients.

Three levels of participation exist in creating successful change:

1) Active working teams are responsible for daily planning, documentation, communication, education, monitoring, and evaluation of activities. The working team must have representation from all departments involved in the change processes ICU, ED, pulmonary department, pharmacy, etc. The team should also be multidisciplinary, comprising physicians, nurses, pharmacists, respiratory therapists, and other staff with roles in the specific change process, such as clerks and technicians. Team members should be knowledgeable about the specific aims, the current local work processes, the associated literature, and any environmental issues that will be affected by these changes.

2) A leadership group or person within the team helps remove barriers, provides resources, monitors global progress, and gives suggestions from an institutional perspective. The working team needs someone with authority in the organization to overcome barriers and to allocate the time and resources the team needs to achieve its aim. Leadership needs to understand how the proposed changes will affect various parts of the system and the more remote consequences such changes might trigger.

3) Providers and stakeholders must be kept informed. Procedures are needed to keep them informed, to receive their feedback, and to ensure them that their responses are respected. This gives stakeholders a sense of ownership and facilitates implementation of the new processes.

click for large version

Protocols

Teams should use the bundles to create customized protocols and pathways that will function well within their institutions. However, all of the elements in the bundles must be incorporated into the protocols. The protocols should mirror the bundles but allow flexibility to accommodate the specific needs of a local hospital. The severe sepsis bundles (and thereby the hospital’s protocol) form the basis for the measurements the team will conduct. If all of the elements of the bundles are not incorporated into your customized protocol, your performance on the measures will suffer.

A strong protocol will accomplish all of the items listed in the severe sepsis bundles. If the protocol designer pays careful attention to the details in the bundles, the protocol will score well on the severe sepsis quality indicators. Hospitals will want to publicize their efforts with regard to improving sepsis care and make the protocol an integral part of their rollout strategy. It is imperative to launch an educational initiative regarding the effort.

Examples of sepsis screening and management protocols are available on the Surviving Sepsis Campaign IHI Web site and are rendered on this page as “Protocol A: Create a protocol and educate users” and as “Prot0col B.” The easiest way to get to that page of the IHI Web site is through the home page link from the Surviving Sepsis Campaign Web site, www.survivingsepsis.org. These highly visual and easy-to-follow pathways exemplify ways to encourage adherence to a protocol. Notice that the “Sepsis Screening Protocol” (p. 25) complies with the terms of the severe sepsis bundles. Posting these types of algorithms prominently in the ED, hospital wards, and ICU, and making them readily available in laminated and PDA format, can have a significant impact on performance improvement programs.

These flow diagrams may be incorporated into lectures and training programs to support your efforts to change care at the bedside. You can adapt the algorithms to fit the needs of your individual institution, but keep in mind the need to comply with the overall structure of the severe sepsis bundles.

click for large version

Data Collection

Data collection can seem like an onerous duty in any quality improvement project. Nevertheless, it is essential for improvement. Without attention to measurement, how will you know that your efforts are leading to improvement? At most hospitals, the magnitude of the data collection effort will not be huge as it will be relative to the number of severely septic patients cared for in the ICU.

Generally, hospitals report three to four severely septic patients are treated in one week’s time. This means that zero, one, or two severely septic patients’ charts will need to be abstracted each day in an average-size hospital. If abstraction takes between 20–30 minutes per chart, the daily time for this effort may range from 30–90 minutes daily. This relatively small burden is likely to represent an initial challenge to anyone unfamiliar with the organization of the chart and the measurement forms, or tools, used by the Surviving Sepsis Campaign for data collection. In time, however, data collection will become easier as the chart and the tools provided by the Surviving Sepsis Campaign will become more familiar. Bundle implementation and data collection have begun in hospitals throughout Europe, Latin America, the United Kingdom, and the United States.

The measurement tools were created to achieve a uniform system of data gathering, collation, and calculation across hospitals. Without the measurement tools, teams armed with only the concepts in the severe sepsis bundles would need to decide how to gather data from charts and put it in a format consistent with the calculations listed in the severe sepsis quality indicators. If any hospital were to undertake such a task on its own, it would quickly find that its results were not comparable across institutions because scores of other hospitals would have derived their results by entirely different means.

The Surviving Sepsis Campaign aims to make using the measurement tools as easy as possible for those involved in collecting data. Several basic tools organize data from the patient’s chart. Initially, a paper set of measurement tools was developed to help hospitals orchestrate data collection. Although a database now performs much of the work formerly done on paper, some use of paper tools may be helpful.

For example, the Surviving Sepsis Campaign’s screening tool for severe sepsis is integrated into the database. However, a paper version readily accessible to nurses and clinicians in the ED triage area, the medical and surgical nursing stations, and even the ICU itself will still be practical.

Likewise, some data collectors might find that first capturing on paper the data abstracted from the chart and subsequently entering it into the database is preferable. Most users are likely to find, however, that bringing the database to the ICU on a laptop and directly entering data is the easiest solution.

The most up-to-date paper versions of the tools and the Surviving Sepsis Campaign database can be found on the Institute of Healthcare Improvement Web site. The easiest way to get to that page of the Institute of Healthcare Improvement Web site is by home page linkage from the Surviving Sepsis Campaign Web site, www.survivingsepsis.org. An implementation manual is also available that will facilitate initiation of the Surviving Sepsis Campaign performance improvement program as well as installation and use of the associated electronic database.

Conclusion

The Surviving Sepsis Campaign represents an important step for international critical care societies. Recognizing the long history of delay in incorporating research into bedside care, these critical care societies have committed to working together to facilitate bench-to-bedside transfer of recent research. Thus, the campaign represents an ongoing commitment to excellence in patient care. The Surviving Sepsis Campaign has established a target of a 25% reduction in mortality worldwide from sepsis over the next five years. If the Surviving Sepsis Campaign is able to bring the guidelines into routine use, it is possible to achieve this goal. For the campaign to be successful, it will require more than good publicity. It will require a further commitment from bedside clinicians to appraise new research critically and adopt interventions proven to be effective rapidly.

Hospitalists interested in more information about instituting the Surviving Sepsis Campaign and performance improvement package in their hospital should e-mail the Surviving Sepsis Campaign user group program manager at dskbranch@mac.com. TH

References

1. Angus DC, Linde-Zwirble WT, Lidicer J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303-1310.
2. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-1377.
3. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862-871.
4. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344(10)699-709.
5. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342:1301-1308.
6. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion in critical care. N Engl J Med. 1999;340:409-4178.
7. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359-1367.
8. Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in medical patients with enoxaparin study group. N Engl J Med. 1999;341:793-800.
9. Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med. 1998;338:791-797.
10. Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-873.
11. Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004;30:536-55.
12. Levy MM, Pronovost PJ, Dellinger RP, et al. Sepsis change bundles: converting guidelines into meaningful change in behavior and clinical outcome. Crit Care Med. 2004;32(suppl):S595-S597.

The incidence of severe sepsis (sepsis with organ dysfunction) is increasing.1 The initial diagnosis and management of severe sepsis may occur in the ED, the ICU, or the hospital ward.

Several recently published studies have demonstrated decreased mortality and morbidity as a result of interventions and therapeutics applied to patients with sepsis.2-5 These new data, resulting from rigorously performed, randomized controlled trials, combined with previous data for beneficial interventions not specific to sepsis management (such as DVT and stress ulcer prophylaxis) and consensus opinion where no evidence exists lend significant weight to the belief that critical care clinicians can now significantly reduce mortality in patients with severe sepsis and septic shock.6-9

Protocolized care now exists for heart attack and stroke, which is based on recent advances as demonstrated by the medical literature. Until now there has been no attempt to reproduce such an approach in severe sepsis. The Surviving Sepsis Campaign hopes to change that.

The Surviving Sepsis Campaign is administered by the Society of Critical Care Medicine (SCCM), the European Society of Intensive Care Medicine (ESICM), and the International Sepsis Forum (ISF) and is open to all industry for funding through unrestricted educational grants. Contributors to date include Baxter, Edwards, and Eli Lilly.

The first phase was the introduction of the campaign at several major international critical care medicine conferences, the ESICM meeting in Barcelona in 2002, and the SCCM meeting in 2003. The stated goal of the campaign is to decrease the mortality from severe sepsis by 25% in five years.

Phase 2 of the campaign was aimed at producing guidelines for the management of sepsis. In 2003, critical care and infectious disease experts representing 11 international organizations developed evidence-based management guidelines for severe sepsis and septic shock for practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign.

Pediatric considerations were provided to contrast adult and pediatric management. The resulting recommendations represent an attempt to facilitate a rapid change in the standard of care for management of sepsis, based on the quality of available published data and expert opinion where no literature guidance is available. The guidelines manuscript was published in both Critical Care Medicine and Intensive Care Medicine.10,11 The publication of this manuscript represents an historic step for critical care worldwide. These guidelines represent an international consensus on the best available standard for management of sepsis.

Key Recommendations

Key recommendations (listed by category and not by hierarchy) include:

• Early goal-directed resuscitation of the septic patient during the first six hours after recognition;
• Appropriate diagnostic studies to ascertain causative organisms before starting antibiotics;
• Early administration of broad-spectrum antibiotic therapy;
• Reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate;
• A usual seven to 10 days of antibiotic therapy guided by clinical response;
• Source control with attention to the method that balances risks and benefits;
• Equivalence of crystalloid and colloid resuscitation;
• Aggressive fluid challenge to restore mean circulating filling pressure;
• Vasopressor preference for norepinephrine and dopamine;
• Cautious use of vasopressin pending further studies;
• Avoidance of low-dose dopamine administration for renal protection;
• Consideration of dobutamine inotropic therapy in some clinical situations;
• Avoidance of supranormal oxygen delivery as a goal of therapy;
• Stress-dose steroid therapy for septic shock;
• Use of recombinant activated protein C in patients with severe sepsis and high risk for death;
• Resolution of tissue hypoperfusion and targeting a hemoglobin of 7-9 g/dL in the absence of coronary artery disease or acute hemorrhage;
• Appropriate use of fresh frozen plasma and platelets;
• A low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome;
• Application of a minimal amount of positive end expiratory pressure in acute lung injury/acute respiratory distress syndrome;
• A semi-recumbent bed position unless contraindicated;
• Protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening;
• Avoidance of neuromuscular blockers, if at all possible;
• Maintenance of blood glucose <150 mg/dL after initial stabilization;
• Equivalence of continuous veno-veno hemofiltration (CVVH) and intermittent hemodialysis;
• Lack of utility of bicarbonate use for pH 7.15 or greater;
• Use of DVT/stress ulcer prophylaxis; and
• Consideration of limitation of support where appropriate.

Pediatric considerations include a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40-60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic endpoints; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control.

Operationalizing the Guidelines

Unfortunately, clinicians change slowly. Historically, transfer of research from the bench to the bedside is a long, tortuous process—one that is not driven by anything clear and that seems to be based more on fad and coincidence than on a keen, evidence-based evaluation of the literature. Phase 3 of the campaign hopes to change that.

Phase 3 of the campaign (www.survivingsepsis.org) aims to operationalize the guidelines to create a global standard of care for sepsis management.12 The guidelines will be transformed into user-friendly tools that allow clinicians to easily incorporate these new recommendations into bedside care. The first step in this next phase has been a joint effort with the Institute of Healthcare Improvement (IHI) to deploy a “change bundle” based on a core set of the previous recommendations into the IHI’s collaborative system. Chart review or concurrent data gathering will identify and track changes in practice and clinical outcomes. Engendering evidence-based change through motivational strategies while monitoring and sharing the results with healthcare practitioners is the key to improving outcomes in severe sepsis.

The severe sepsis bundles form the core of the Surviving Sepsis Campaign. A “bundle” is a group of interventions related to a disease process. When executed together, the interventions produce better outcomes than when implemented individually. The individual bundle elements are built on evidence-based practices. The science behind the elements of a bundle is so well established that their implementation should be considered a generally accepted practice. Develop a bundle process in the following way:

1. Identify a set of four to six evidence-based interventions that apply to a cohort of patients with a common disease or a common location. An example might be patients with sepsis admitted to the ICU;
2. Develop the will in the providers to deliver the interventions every time they are indicated;
3. Redesign the delivery system to ensure the interventions in the bundle are delivered; and
4. Measure related outcomes to ascertain the effects of the changes in the delivery system.

The sepsis bundles were developed in just such a manner, based on the experience of the ventilator bundle. The goal now is to motivate providers to deliver the sepsis interventions every time they are indicated and measure them in an all-or-nothing way. We believe that if the bundle elements are reliably performed we can achieve the desired outcome of reducing sepsis-related deaths by 25%.

These elements distill the Surviving Sepsis Campaign practice guidelines into a manageable format for use at most institutions. The bundles represent the specific changes the campaign has identified as essential to the care of severely septic patients. Following the severe sepsis bundles will eliminate the piecemeal or inappropriate application of standards for sepsis care that characterize most clinical environments today.

Hospitals should implement two different severe sepsis bundles. Each bundle articulates objectives to be accomplished within specific time frames.

Sepsis Resuscitation Bundle

The severe sepsis resuscitation bundle describes seven tasks that should begin immediately but must be accomplished within the first six hours of presentation for patients with severe sepsis or septic shock. Some items may not be completed if the clinical conditions described in the bundle do not prevail in a particular case, but clinicians must assess for them. The goal is to perform all indicated tasks 100% of the time within the first six hours of identification of severe sepsis. The tasks are:

1. Measure serum lactate;
2. Obtain blood cultures prior to antibiotic administration;
3. Administer broad-spectrum antibiotics within three hours from time of presentation for ED admissions and one hour for non-ED ICU admissions;
4. In the event of hypotension and/or lactate >4 mmol/L (36 mg/dL):

   1. Deliver an initial minimum of 20 ml/kg of crystalloid (or colloid equivalent); and
   2. Apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) ≥65 mm Hg;

5. In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/L (36 mg/dL):

   1. Achieve central venous pressure (CVP) of ≥8-12 mm Hg; and
   2. Achieve central venous oxygen saturation (ScvO2) of Surviving Sepsis Campaign70%. (Achieving a mixed venous oxygen saturation (SvO2) of 65% is an acceptable alternative.)

Sepsis Management Bundle

The severe sepsis management bundle lists four management goals. Efforts to accomplish these tasks should also begin immediately, but these items may be completed within 24 hours of presentation for patients with severe sepsis or septic shock.

1. Administer low-dose steroids for septic shock in accordance with a standardized ICU policy;
2. Administer drotrecogin alfa (activated) in accordance with a standardized ICU policy;
3. Maintain glucose control ≥ lower limit of normal, but <150 mg/dL (8.3 mmol/L); and
4. Maintain inspiratory plateau pressures <30 cm H2O for mechanically ventilated patients.

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Team Effort

To achieve the goal of reducing mortality by 25% by 2008, everyone involved with the care of severe sepsis patients must be included, work processes must be carefully scripted and standardized, and commitment to this effort must be elevated. This must be a team effort that crosses disciplines and departments; it requires leadership, support from the entire organization, and buy-in from all stakeholders involved with the care of these patients.

Three levels of participation exist in creating successful change:

1) Active working teams are responsible for daily planning, documentation, communication, education, monitoring, and evaluation of activities. The working team must have representation from all departments involved in the change processes ICU, ED, pulmonary department, pharmacy, etc. The team should also be multidisciplinary, comprising physicians, nurses, pharmacists, respiratory therapists, and other staff with roles in the specific change process, such as clerks and technicians. Team members should be knowledgeable about the specific aims, the current local work processes, the associated literature, and any environmental issues that will be affected by these changes.

2) A leadership group or person within the team helps remove barriers, provides resources, monitors global progress, and gives suggestions from an institutional perspective. The working team needs someone with authority in the organization to overcome barriers and to allocate the time and resources the team needs to achieve its aim. Leadership needs to understand how the proposed changes will affect various parts of the system and the more remote consequences such changes might trigger.

3) Providers and stakeholders must be kept informed. Procedures are needed to keep them informed, to receive their feedback, and to ensure them that their responses are respected. This gives stakeholders a sense of ownership and facilitates implementation of the new processes.

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Protocols

Teams should use the bundles to create customized protocols and pathways that will function well within their institutions. However, all of the elements in the bundles must be incorporated into the protocols. The protocols should mirror the bundles but allow flexibility to accommodate the specific needs of a local hospital. The severe sepsis bundles (and thereby the hospital’s protocol) form the basis for the measurements the team will conduct. If all of the elements of the bundles are not incorporated into your customized protocol, your performance on the measures will suffer.

A strong protocol will accomplish all of the items listed in the severe sepsis bundles. If the protocol designer pays careful attention to the details in the bundles, the protocol will score well on the severe sepsis quality indicators. Hospitals will want to publicize their efforts with regard to improving sepsis care and make the protocol an integral part of their rollout strategy. It is imperative to launch an educational initiative regarding the effort.

Examples of sepsis screening and management protocols are available on the Surviving Sepsis Campaign IHI Web site and are rendered on this page as “Protocol A: Create a protocol and educate users” and as “Prot0col B.” The easiest way to get to that page of the IHI Web site is through the home page link from the Surviving Sepsis Campaign Web site, www.survivingsepsis.org. These highly visual and easy-to-follow pathways exemplify ways to encourage adherence to a protocol. Notice that the “Sepsis Screening Protocol” (p. 25) complies with the terms of the severe sepsis bundles. Posting these types of algorithms prominently in the ED, hospital wards, and ICU, and making them readily available in laminated and PDA format, can have a significant impact on performance improvement programs.

These flow diagrams may be incorporated into lectures and training programs to support your efforts to change care at the bedside. You can adapt the algorithms to fit the needs of your individual institution, but keep in mind the need to comply with the overall structure of the severe sepsis bundles.

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Data Collection

Data collection can seem like an onerous duty in any quality improvement project. Nevertheless, it is essential for improvement. Without attention to measurement, how will you know that your efforts are leading to improvement? At most hospitals, the magnitude of the data collection effort will not be huge as it will be relative to the number of severely septic patients cared for in the ICU.

Generally, hospitals report three to four severely septic patients are treated in one week’s time. This means that zero, one, or two severely septic patients’ charts will need to be abstracted each day in an average-size hospital. If abstraction takes between 20–30 minutes per chart, the daily time for this effort may range from 30–90 minutes daily. This relatively small burden is likely to represent an initial challenge to anyone unfamiliar with the organization of the chart and the measurement forms, or tools, used by the Surviving Sepsis Campaign for data collection. In time, however, data collection will become easier as the chart and the tools provided by the Surviving Sepsis Campaign will become more familiar. Bundle implementation and data collection have begun in hospitals throughout Europe, Latin America, the United Kingdom, and the United States.

The measurement tools were created to achieve a uniform system of data gathering, collation, and calculation across hospitals. Without the measurement tools, teams armed with only the concepts in the severe sepsis bundles would need to decide how to gather data from charts and put it in a format consistent with the calculations listed in the severe sepsis quality indicators. If any hospital were to undertake such a task on its own, it would quickly find that its results were not comparable across institutions because scores of other hospitals would have derived their results by entirely different means.

The Surviving Sepsis Campaign aims to make using the measurement tools as easy as possible for those involved in collecting data. Several basic tools organize data from the patient’s chart. Initially, a paper set of measurement tools was developed to help hospitals orchestrate data collection. Although a database now performs much of the work formerly done on paper, some use of paper tools may be helpful.

For example, the Surviving Sepsis Campaign’s screening tool for severe sepsis is integrated into the database. However, a paper version readily accessible to nurses and clinicians in the ED triage area, the medical and surgical nursing stations, and even the ICU itself will still be practical.

Likewise, some data collectors might find that first capturing on paper the data abstracted from the chart and subsequently entering it into the database is preferable. Most users are likely to find, however, that bringing the database to the ICU on a laptop and directly entering data is the easiest solution.

The most up-to-date paper versions of the tools and the Surviving Sepsis Campaign database can be found on the Institute of Healthcare Improvement Web site. The easiest way to get to that page of the Institute of Healthcare Improvement Web site is by home page linkage from the Surviving Sepsis Campaign Web site, www.survivingsepsis.org. An implementation manual is also available that will facilitate initiation of the Surviving Sepsis Campaign performance improvement program as well as installation and use of the associated electronic database.

Conclusion

The Surviving Sepsis Campaign represents an important step for international critical care societies. Recognizing the long history of delay in incorporating research into bedside care, these critical care societies have committed to working together to facilitate bench-to-bedside transfer of recent research. Thus, the campaign represents an ongoing commitment to excellence in patient care. The Surviving Sepsis Campaign has established a target of a 25% reduction in mortality worldwide from sepsis over the next five years. If the Surviving Sepsis Campaign is able to bring the guidelines into routine use, it is possible to achieve this goal. For the campaign to be successful, it will require more than good publicity. It will require a further commitment from bedside clinicians to appraise new research critically and adopt interventions proven to be effective rapidly.

Hospitalists interested in more information about instituting the Surviving Sepsis Campaign and performance improvement package in their hospital should e-mail the Surviving Sepsis Campaign user group program manager at dskbranch@mac.com. TH

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