Charles D Pham, MD

Upper gastrointestinal bleeding (UGIB) is defined as a bleed originating from the esophagus, stomach, or duodenum. Approximately 80% of patients with UGIB presenting to the emergency department are admitted to the hospital, accounting for more than 200,000 hospital admissions and 4000 in-hospital deaths per year.¹ In this article, we highlight 9 of the 16 recommendations from the 2021 American College of Gastroenterology (ACG) guidelines that are most pertinent to the hospitalist, presented in sections corresponding to the stages of inpatient clinical management.

Initial Triage

Recommendation 1. Patients with UGIB presenting to the emergency department who are classified as very low risk, defined as a risk assessment score with ≤1% false-negative rate for the outcome of hospital-based intervention or death (ie, Glasgow-Blatchford score of 0-1), should be discharged with outpatient follow-up rather than admitted to the hospital (conditional recommendation, very-low-quality evidence). The Glasgow-Blatchford score is an effective risk-assessment tool that can classify patients at high risk for death or needing a hospital-based intervention (eg, endoscopy or blood transfusion) with a sensitivity of 99%.² Triage decisions should incorporate other patient factors, such as age, comorbidities, and reliability of close follow-up after discharge.

Pre-endoscopy Management

Recommendation 2. A restrictive threshold for red blood cell transfusion of 7 g/dL is recommended for patients with UGIB (conditional recommendation, low-quality evidence) as it appears to reduce death and further bleeding.³ It is reasonable to transfuse patients with preexisting cardiovascular disease whose hemoglobin is below 8 g/dL. For patients who are exsanguinating with hemodynamic instability, it is reasonable to transfuse before the hemoglobin reaches 7 g/dL.

Recommendation 3. An infusion of erythromycin is recommended before endoscopy in patients with UGIB (conditional recommendation, very-low-quality evidence). Erythromycin (250 mg intravenously [IV]) improves endoscopic visualization and diagnostic accuracy by moving the blood and clot out of the upper GI tract. A meta-analysis showed a reduction of need for repeat endoscopy (odds ratio [OR], 0.51; 95% CI, 0.34-0.77) and length of hospitalization (mean difference, –1.75 d).⁴

Recommendation 4. There is no consensus for or against pre-endoscopic proton pump inhibitor (PPI) therapy for patients with UGIB, owing to overall limited available data.

Recommendation 5. Patients hospitalized for UGIB should undergo endoscopy within 24 hours of presentation (conditional recommendation, very-low-quality evidence). Performing endoscopy within 24 hours, rather than 12 hours, of presentation demonstrated a potential trend toward decreased length of stay, mortality, and need for surgery. The potential harm in performing earlier endoscopy was attributed to inadequate resuscitation and insufficient optimization of active comorbidities.

Post-endoscopy Management

Recommendation 6. High-dose PPI therapy should be given for 3 days after successful endoscopic hemostatic therapy of a bleeding ulcer (strong recommendation, moderate- to high-quality evidence). When compared with placebo, there is an absolute risk reduction of 3% in mortality and 10% in further bleeding when administering continuous (80 mg bolus with 8 mg/h infusion) or intermittent high-dose PPI therapy (80 mg bolus with 40 mg 2-4 times daily thereafter) for 3 days after endoscopic therapy.^5,6 Cost and ease of administration should be considered when choosing between intermittent or continuous PPI therapy. Oral PPI therapy may be appropriate for patients who are able to tolerate oral intake (no nausea, vomiting, dysphagia, or somnolence).

Recommendation 7. High-risk patients (defined as a Rockall score of ≥6 ) with UGIB due to ulcers who received endoscopic hemostatic therapy followed by short-term high-dose PPI therapy in hospital should be continued on twice-daily PPI therapy until 2 weeks after index endoscopy (conditional recommendation, low-quality evidence). A randomized controlled trial of high-risk patients showed significantly lower recurrence of bleeding with twice-daily vs once daily PPI.⁷ It remains uncertain whether patients benefit from PPI therapy beyond 4 weeks.

Rebleeding Management

Recommendation 8. Patients with recurrent bleeding after endoscopic therapy for a bleeding ulcer should undergo repeat endoscopic therapy rather than surgery or transcatheter arterial embolization (TAE) (conditional recommendation, low-quality evidence for comparison with surgery, very-low-quality evidence for comparison with TAE). In a small randomized controlled trial of repeat endoscopy vs surgery in patients with rebleeding after initial successful endoscopic treatment, there were more subsequent bleeding episodes in the repeat endoscopy group, but no significant difference in mortality and length of stay.⁸ The repeat endoscopy group had fewer complications, though, and a successful treatment rate of 75%. Because of the lack of high-quality studies in support of TAE and the known safety and efficacy of repeat endoscopy, repeat endoscopy is preferred over TAE for recurrent UGIB.

Recommendation 9. Patients with bleeding ulcers who have failed repeat endoscopic therapy should be treated with TAE (conditional recommendation, very-low-quality evidence). Based on a meta-analysis, when comparing TAE with surgery in patients with UGIB who fail endoscopic therapy, overall mortality was the same, and TAE patients had fewer complications and shorter hospital stays despite having a higher risk of further bleeding.⁹

The guidelines were formulated by panel members with input from the ACG Practice Parameters Committee using the population, intervention, comparator, and outcome (PICO) format to frame each question. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the strength of the recommendation and the quality of evidence.

Most of the recommendations are conditional and/or based on low-quality or very-low-quality evidence. Although randomized control trials were sought, observational studies were sometimes included when randomized controlled trials were lacking. The literature review process appeared to focus on the primary outcome of further bleeding, which, although critical in patients with UGIB, could have limited the scope of evidence used in making the recommendations. It was stated that studies identified as relevant to the panel members or authors were considered for review without mentioning any standardized approach. The composition of the panel members was not discussed, and it is uncertain whether the guidelines underwent any formal peer-review process. Furthermore, although competing interests were declared, the panel did not discuss how conflicts were managed and what potential impact they had in the guideline recommendations. Finally, some of the recommendations (eg, TAE) will depend on local expertise and may not be available at all medical centers.

Further study is needed to address the integration of risk-assessment tools into electronic health records to assist with timely decisions on managing patients with acute UGIB, to clarify the role for pre-endoscopic PPI therapy, and to specify fluid resuscitation and blood pressure goals in patients with more severe bleeding episodes and determine whether a subset of patients might benefit from very-early endoscopy (the 2012 ACG guidelines suggested that endoscopy within 12 hours may be considered in patients with high-risk clinical features such as hemodynamic instability or cirrhosis).

Glasgow-Blatchford Score (https://www.mdcalc.com/glasgow-blatchford-bleeding-score-gbs)

Rockall Score (https://www.mdcalc.com/rockall-score-upper-gi-bleeding-pre-endoscopy)

Upper gastrointestinal bleeding (UGIB) is defined as a bleed originating from the esophagus, stomach, or duodenum. Approximately 80% of patients with UGIB presenting to the emergency department are admitted to the hospital, accounting for more than 200,000 hospital admissions and 4000 in-hospital deaths per year.¹ In this article, we highlight 9 of the 16 recommendations from the 2021 American College of Gastroenterology (ACG) guidelines that are most pertinent to the hospitalist, presented in sections corresponding to the stages of inpatient clinical management.

Initial Triage

Recommendation 1. Patients with UGIB presenting to the emergency department who are classified as very low risk, defined as a risk assessment score with ≤1% false-negative rate for the outcome of hospital-based intervention or death (ie, Glasgow-Blatchford score of 0-1), should be discharged with outpatient follow-up rather than admitted to the hospital (conditional recommendation, very-low-quality evidence). The Glasgow-Blatchford score is an effective risk-assessment tool that can classify patients at high risk for death or needing a hospital-based intervention (eg, endoscopy or blood transfusion) with a sensitivity of 99%.² Triage decisions should incorporate other patient factors, such as age, comorbidities, and reliability of close follow-up after discharge.

Pre-endoscopy Management

Recommendation 2. A restrictive threshold for red blood cell transfusion of 7 g/dL is recommended for patients with UGIB (conditional recommendation, low-quality evidence) as it appears to reduce death and further bleeding.³ It is reasonable to transfuse patients with preexisting cardiovascular disease whose hemoglobin is below 8 g/dL. For patients who are exsanguinating with hemodynamic instability, it is reasonable to transfuse before the hemoglobin reaches 7 g/dL.

Recommendation 3. An infusion of erythromycin is recommended before endoscopy in patients with UGIB (conditional recommendation, very-low-quality evidence). Erythromycin (250 mg intravenously [IV]) improves endoscopic visualization and diagnostic accuracy by moving the blood and clot out of the upper GI tract. A meta-analysis showed a reduction of need for repeat endoscopy (odds ratio [OR], 0.51; 95% CI, 0.34-0.77) and length of hospitalization (mean difference, –1.75 d).⁴

Recommendation 4. There is no consensus for or against pre-endoscopic proton pump inhibitor (PPI) therapy for patients with UGIB, owing to overall limited available data.

Recommendation 5. Patients hospitalized for UGIB should undergo endoscopy within 24 hours of presentation (conditional recommendation, very-low-quality evidence). Performing endoscopy within 24 hours, rather than 12 hours, of presentation demonstrated a potential trend toward decreased length of stay, mortality, and need for surgery. The potential harm in performing earlier endoscopy was attributed to inadequate resuscitation and insufficient optimization of active comorbidities.

Post-endoscopy Management

Recommendation 6. High-dose PPI therapy should be given for 3 days after successful endoscopic hemostatic therapy of a bleeding ulcer (strong recommendation, moderate- to high-quality evidence). When compared with placebo, there is an absolute risk reduction of 3% in mortality and 10% in further bleeding when administering continuous (80 mg bolus with 8 mg/h infusion) or intermittent high-dose PPI therapy (80 mg bolus with 40 mg 2-4 times daily thereafter) for 3 days after endoscopic therapy.^5,6 Cost and ease of administration should be considered when choosing between intermittent or continuous PPI therapy. Oral PPI therapy may be appropriate for patients who are able to tolerate oral intake (no nausea, vomiting, dysphagia, or somnolence).

Recommendation 7. High-risk patients (defined as a Rockall score of ≥6 ) with UGIB due to ulcers who received endoscopic hemostatic therapy followed by short-term high-dose PPI therapy in hospital should be continued on twice-daily PPI therapy until 2 weeks after index endoscopy (conditional recommendation, low-quality evidence). A randomized controlled trial of high-risk patients showed significantly lower recurrence of bleeding with twice-daily vs once daily PPI.⁷ It remains uncertain whether patients benefit from PPI therapy beyond 4 weeks.

Rebleeding Management

Recommendation 8. Patients with recurrent bleeding after endoscopic therapy for a bleeding ulcer should undergo repeat endoscopic therapy rather than surgery or transcatheter arterial embolization (TAE) (conditional recommendation, low-quality evidence for comparison with surgery, very-low-quality evidence for comparison with TAE). In a small randomized controlled trial of repeat endoscopy vs surgery in patients with rebleeding after initial successful endoscopic treatment, there were more subsequent bleeding episodes in the repeat endoscopy group, but no significant difference in mortality and length of stay.⁸ The repeat endoscopy group had fewer complications, though, and a successful treatment rate of 75%. Because of the lack of high-quality studies in support of TAE and the known safety and efficacy of repeat endoscopy, repeat endoscopy is preferred over TAE for recurrent UGIB.

Recommendation 9. Patients with bleeding ulcers who have failed repeat endoscopic therapy should be treated with TAE (conditional recommendation, very-low-quality evidence). Based on a meta-analysis, when comparing TAE with surgery in patients with UGIB who fail endoscopic therapy, overall mortality was the same, and TAE patients had fewer complications and shorter hospital stays despite having a higher risk of further bleeding.⁹

The guidelines were formulated by panel members with input from the ACG Practice Parameters Committee using the population, intervention, comparator, and outcome (PICO) format to frame each question. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the strength of the recommendation and the quality of evidence.

Most of the recommendations are conditional and/or based on low-quality or very-low-quality evidence. Although randomized control trials were sought, observational studies were sometimes included when randomized controlled trials were lacking. The literature review process appeared to focus on the primary outcome of further bleeding, which, although critical in patients with UGIB, could have limited the scope of evidence used in making the recommendations. It was stated that studies identified as relevant to the panel members or authors were considered for review without mentioning any standardized approach. The composition of the panel members was not discussed, and it is uncertain whether the guidelines underwent any formal peer-review process. Furthermore, although competing interests were declared, the panel did not discuss how conflicts were managed and what potential impact they had in the guideline recommendations. Finally, some of the recommendations (eg, TAE) will depend on local expertise and may not be available at all medical centers.

Further study is needed to address the integration of risk-assessment tools into electronic health records to assist with timely decisions on managing patients with acute UGIB, to clarify the role for pre-endoscopic PPI therapy, and to specify fluid resuscitation and blood pressure goals in patients with more severe bleeding episodes and determine whether a subset of patients might benefit from very-early endoscopy (the 2012 ACG guidelines suggested that endoscopy within 12 hours may be considered in patients with high-risk clinical features such as hemodynamic instability or cirrhosis).

Glasgow-Blatchford Score (https://www.mdcalc.com/glasgow-blatchford-bleeding-score-gbs)

Rockall Score (https://www.mdcalc.com/rockall-score-upper-gi-bleeding-pre-endoscopy)

Upper gastrointestinal bleeding (UGIB) is defined as a bleed originating from the esophagus, stomach, or duodenum. Approximately 80% of patients with UGIB presenting to the emergency department are admitted to the hospital, accounting for more than 200,000 hospital admissions and 4000 in-hospital deaths per year.¹ In this article, we highlight 9 of the 16 recommendations from the 2021 American College of Gastroenterology (ACG) guidelines that are most pertinent to the hospitalist, presented in sections corresponding to the stages of inpatient clinical management.

Initial Triage

Recommendation 1. Patients with UGIB presenting to the emergency department who are classified as very low risk, defined as a risk assessment score with ≤1% false-negative rate for the outcome of hospital-based intervention or death (ie, Glasgow-Blatchford score of 0-1), should be discharged with outpatient follow-up rather than admitted to the hospital (conditional recommendation, very-low-quality evidence). The Glasgow-Blatchford score is an effective risk-assessment tool that can classify patients at high risk for death or needing a hospital-based intervention (eg, endoscopy or blood transfusion) with a sensitivity of 99%.² Triage decisions should incorporate other patient factors, such as age, comorbidities, and reliability of close follow-up after discharge.

Pre-endoscopy Management

Recommendation 2. A restrictive threshold for red blood cell transfusion of 7 g/dL is recommended for patients with UGIB (conditional recommendation, low-quality evidence) as it appears to reduce death and further bleeding.³ It is reasonable to transfuse patients with preexisting cardiovascular disease whose hemoglobin is below 8 g/dL. For patients who are exsanguinating with hemodynamic instability, it is reasonable to transfuse before the hemoglobin reaches 7 g/dL.

Recommendation 3. An infusion of erythromycin is recommended before endoscopy in patients with UGIB (conditional recommendation, very-low-quality evidence). Erythromycin (250 mg intravenously [IV]) improves endoscopic visualization and diagnostic accuracy by moving the blood and clot out of the upper GI tract. A meta-analysis showed a reduction of need for repeat endoscopy (odds ratio [OR], 0.51; 95% CI, 0.34-0.77) and length of hospitalization (mean difference, –1.75 d).⁴

Recommendation 4. There is no consensus for or against pre-endoscopic proton pump inhibitor (PPI) therapy for patients with UGIB, owing to overall limited available data.

Recommendation 5. Patients hospitalized for UGIB should undergo endoscopy within 24 hours of presentation (conditional recommendation, very-low-quality evidence). Performing endoscopy within 24 hours, rather than 12 hours, of presentation demonstrated a potential trend toward decreased length of stay, mortality, and need for surgery. The potential harm in performing earlier endoscopy was attributed to inadequate resuscitation and insufficient optimization of active comorbidities.

Post-endoscopy Management

Recommendation 6. High-dose PPI therapy should be given for 3 days after successful endoscopic hemostatic therapy of a bleeding ulcer (strong recommendation, moderate- to high-quality evidence). When compared with placebo, there is an absolute risk reduction of 3% in mortality and 10% in further bleeding when administering continuous (80 mg bolus with 8 mg/h infusion) or intermittent high-dose PPI therapy (80 mg bolus with 40 mg 2-4 times daily thereafter) for 3 days after endoscopic therapy.^5,6 Cost and ease of administration should be considered when choosing between intermittent or continuous PPI therapy. Oral PPI therapy may be appropriate for patients who are able to tolerate oral intake (no nausea, vomiting, dysphagia, or somnolence).

Recommendation 7. High-risk patients (defined as a Rockall score of ≥6 ) with UGIB due to ulcers who received endoscopic hemostatic therapy followed by short-term high-dose PPI therapy in hospital should be continued on twice-daily PPI therapy until 2 weeks after index endoscopy (conditional recommendation, low-quality evidence). A randomized controlled trial of high-risk patients showed significantly lower recurrence of bleeding with twice-daily vs once daily PPI.⁷ It remains uncertain whether patients benefit from PPI therapy beyond 4 weeks.

Rebleeding Management

Recommendation 8. Patients with recurrent bleeding after endoscopic therapy for a bleeding ulcer should undergo repeat endoscopic therapy rather than surgery or transcatheter arterial embolization (TAE) (conditional recommendation, low-quality evidence for comparison with surgery, very-low-quality evidence for comparison with TAE). In a small randomized controlled trial of repeat endoscopy vs surgery in patients with rebleeding after initial successful endoscopic treatment, there were more subsequent bleeding episodes in the repeat endoscopy group, but no significant difference in mortality and length of stay.⁸ The repeat endoscopy group had fewer complications, though, and a successful treatment rate of 75%. Because of the lack of high-quality studies in support of TAE and the known safety and efficacy of repeat endoscopy, repeat endoscopy is preferred over TAE for recurrent UGIB.

Recommendation 9. Patients with bleeding ulcers who have failed repeat endoscopic therapy should be treated with TAE (conditional recommendation, very-low-quality evidence). Based on a meta-analysis, when comparing TAE with surgery in patients with UGIB who fail endoscopic therapy, overall mortality was the same, and TAE patients had fewer complications and shorter hospital stays despite having a higher risk of further bleeding.⁹

The guidelines were formulated by panel members with input from the ACG Practice Parameters Committee using the population, intervention, comparator, and outcome (PICO) format to frame each question. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the strength of the recommendation and the quality of evidence.

Most of the recommendations are conditional and/or based on low-quality or very-low-quality evidence. Although randomized control trials were sought, observational studies were sometimes included when randomized controlled trials were lacking. The literature review process appeared to focus on the primary outcome of further bleeding, which, although critical in patients with UGIB, could have limited the scope of evidence used in making the recommendations. It was stated that studies identified as relevant to the panel members or authors were considered for review without mentioning any standardized approach. The composition of the panel members was not discussed, and it is uncertain whether the guidelines underwent any formal peer-review process. Furthermore, although competing interests were declared, the panel did not discuss how conflicts were managed and what potential impact they had in the guideline recommendations. Finally, some of the recommendations (eg, TAE) will depend on local expertise and may not be available at all medical centers.

Further study is needed to address the integration of risk-assessment tools into electronic health records to assist with timely decisions on managing patients with acute UGIB, to clarify the role for pre-endoscopic PPI therapy, and to specify fluid resuscitation and blood pressure goals in patients with more severe bleeding episodes and determine whether a subset of patients might benefit from very-early endoscopy (the 2012 ACG guidelines suggested that endoscopy within 12 hours may be considered in patients with high-risk clinical features such as hemodynamic instability or cirrhosis).

Glasgow-Blatchford Score (https://www.mdcalc.com/glasgow-blatchford-bleeding-score-gbs)

Rockall Score (https://www.mdcalc.com/rockall-score-upper-gi-bleeding-pre-endoscopy)

Sickle cell disease (SCD) affects an estimated 100,000 people in the United States.¹ Pain is the most common complication of SCD and the primary reason patients with SCD seek medical attention.² In 2016, three-fourths of the approximately 130,000 SCD-related hospitalizations in the United States involved pain crises.³ When managing patients with SCD and chronic pain, an individualized and interdisciplinary approach is crucial. In 2020, the American Society of Hematology (ASH) developed guidelines reflecting the latest evidence in managing acute and chronic pain in adult and pediatric patients with SCD. The ASH guidelines provide 18 recommendations; here, we highlight the 8 recommendations most pertinent to the hospitalist.

Acute Pain

Acute pain in the guideline is defined as pain that results in an unplanned visit to an acute care center for treatment.

Recommendation 1. For adult and pediatric patients presenting to an acute care setting with SCD-related acute pain, the ASH guideline panel recommends rapid (ie, within 1 hour of arrival at the emergency department [ED]) assessment and administration of analgesia, with reassessments every 30-60 minutes to optimize pain control (Strong recommendation; low certainty in the evidence about effects).

Although the perceived benefits are unclear due to insufficient evidence, the panel agrees that delaying pain management results in undeniable harm to patients. Hence, this recommendation was deemed both acceptable and ethical. Rapid evaluation also allows for earlier identification and treatment of other potential SCD-related complications.

Recommendation 2. For adult and pediatric patients presenting to an acute care setting with SCD-associated pain for whom opioid therapy is indicated, the ASH guideline panel suggests tailored opioid dosing based on consideration of baseline opioid therapy and prior effective therapy. (For adults: conditional recommendation; moderate certainty in the evidence about effects. For children: conditional recommendation; low certainty in the evidence about effects).

One randomized controlled trial examined patient-specific opioid dosing (based on current chronic opioid therapy [COT] and previously known effective acute pain management) vs weight-based dosing in the ED and found that participants randomized into the patient-specific protocol had a greater reduction in pain and decreased rate of hospital admission.⁴

The panel acknowledges that intravenous patient-controlled opioid analgesia is generally the standard of care at most institutions. However, no clear data address whether continuous opioid infusion in addition to on-demand dosing is beneficial.

Recommendation 3. For adult and pediatric patients with acute pain related to SCD, the ASH guideline panel suggests a short course (5 to 7 days) of nonsteroidal anti-inflammatory drugs (NSAIDs) in addition to opioids (Conditional recommendation; very low certainty in the evidence about effects).

The use of NSAIDs for managing pain in hospitalized patients with SCD has been associated with a reduction in the use of opioids in the inpatient setting and decreased lengths of stay.⁵ The potential harms of NSAIDs, including renal and gastrointestinal toxicity, however, should be factored into the decision-making as the risks may outweigh the potential benefits.

Recommendation 4. For adult and pediatric patients with SCD hospitalized for acute pain, the ASH guideline panel suggests a subanesthetic (analgesic) infusion of ketamine as adjunctive treatment of pain refractory or not effectively treated with opioids alone (Conditional recommendation; very low certainty in the evidence about effects). The guideline panel also suggests regional anesthesia for localized pain refractory or not effectively treated with opioids alone (Conditional recommendation; very low certainty in the evidence about effects).

Studies have demonstrated reduced pain and opioid utilization in individuals who received adjuvant ketamine infusions⁶ or regional anesthesia (ie, epidural).⁷ Feasibility, however, is limited to centers that have the appropriate experience and expertise with these interventions.

Recommendation 5. For adult and pediatric patients who have recurrent acute pain associated with SCD, the ASH guideline panel suggests against chronic monthly transfusion therapy as a first-line strategy to prevent or reduce recurrent acute pain episodes (Conditional recommendation; low certainty in the evidence about effects). The evidence for monthly transfusions in preventing recurrent pain is limited. There is, however, a moderate risk of harm, including iron overload and transfusion reactions, in addition to substantial burden and costs.

Chronic Pain

Chronic pain in the guideline is defined as ongoing pain present on most days over the past 6 months.

Recommendation 6. For adult patients with SCD who have chronic pain from the SCD-related identifiable cause avascular necrosis (AVN) of the bone, the ASH guideline panel suggests the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) or NSAIDs in the context of a comprehensive disease and pain management plan (Conditional recommendation; very low certainty in the evidence about effects). For patients with no identifiable cause beyond SCD, the guideline panel suggests SNRIs, tricyclic antidepressants, or gabapentinoids for pain management (Conditional recommendation; very low certainty in the evidence about effects). Given the lack of direct evidence, indirect evidence was used to formulate these recommendations. For pain associated with AVN, data were extrapolated from literature on osteoarthritis, a form of degenerative arthropathy. For pain without an identifiable cause, evidence was taken from studies on fibromyalgia, a condition the panel felt most closely aligned with chronic pain related to SCD.

No recommendations were made for pediatric patients as the indirect evidence base only addressed adult patients.

Recommendation 7. For adult and pediatric patients with SCD and emerging and/or recently developed chronic pain, the ASH guideline panel does not recommend initiating COT unless pain is refractory to multiple other treatment modalities (Conditional recommendation; very low certainty in the evidence about effects). For patients receiving COT who are functioning well and have perceived benefit, the ASH guideline panel suggests shared decision-making for continuation of COT (Conditional recommendation; very low certainty in the evidence about effects).

High-quality data on the benefit of long-term COT in individuals with chronic noncancer pain are lacking. The panel maintains that the decision to initiate or continue COT should be individualized after weighing appropriate risks and benefits.

Recommendation 8. For adult and pediatric patients with chronic pain related to SCD, the panel suggests cognitive and behavioral pain management strategies in the context of a comprehensive disease and pain management plan (Conditional recommendation; very low certainty in the evidence about effects). Cognitive behavioral therapy may decrease overall pain intensity and improve coping skills.⁸ The panel agrees that medications alone may not be effective in reducing the burden of chronic pain in adult and pediatric patients with SCD.

The guidelines were created by a multidisciplinary panel that included physicians from hematology, pain medicine, psychiatry, and emergency medicine, a doctoral nurse practitioner, and two patient representatives. The Mayo Evidence-Based Practice Research Program supported the guideline-development process. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to assess evidence and make recommendations.

High-quality data in treating acute and chronic pain in both adult and pediatric patients with SCD are limited. As such, the majority of recommendations in these guidelines are conditional. The panel included studies that were indirectly related to SCD based on consensus (eg, inferred data from disease processes thought to be similar to SCD). One panelist disclosed receiving direct payments from a company that could be affected by these guidelines; however, it was deemed that the conflict was unlikely to have influenced any recommendations.

The panel acknowledges that further investigation is needed for both nonpharmacologic and pharmacologic modalities in treating acute and chronic pain related to SCD. Examples include evaluating the comparative-effectiveness of COT vs nonopioid pharmacotherapy, the benefits and harms of continuous opioid infusions in acute pain crises, and the impact of chronic transfusions on acute and chronic pain.

Sickle cell disease (SCD) affects an estimated 100,000 people in the United States.¹ Pain is the most common complication of SCD and the primary reason patients with SCD seek medical attention.² In 2016, three-fourths of the approximately 130,000 SCD-related hospitalizations in the United States involved pain crises.³ When managing patients with SCD and chronic pain, an individualized and interdisciplinary approach is crucial. In 2020, the American Society of Hematology (ASH) developed guidelines reflecting the latest evidence in managing acute and chronic pain in adult and pediatric patients with SCD. The ASH guidelines provide 18 recommendations; here, we highlight the 8 recommendations most pertinent to the hospitalist.

Acute Pain

Acute pain in the guideline is defined as pain that results in an unplanned visit to an acute care center for treatment.

Recommendation 1. For adult and pediatric patients presenting to an acute care setting with SCD-related acute pain, the ASH guideline panel recommends rapid (ie, within 1 hour of arrival at the emergency department [ED]) assessment and administration of analgesia, with reassessments every 30-60 minutes to optimize pain control (Strong recommendation; low certainty in the evidence about effects).

Although the perceived benefits are unclear due to insufficient evidence, the panel agrees that delaying pain management results in undeniable harm to patients. Hence, this recommendation was deemed both acceptable and ethical. Rapid evaluation also allows for earlier identification and treatment of other potential SCD-related complications.

Recommendation 2. For adult and pediatric patients presenting to an acute care setting with SCD-associated pain for whom opioid therapy is indicated, the ASH guideline panel suggests tailored opioid dosing based on consideration of baseline opioid therapy and prior effective therapy. (For adults: conditional recommendation; moderate certainty in the evidence about effects. For children: conditional recommendation; low certainty in the evidence about effects).

One randomized controlled trial examined patient-specific opioid dosing (based on current chronic opioid therapy [COT] and previously known effective acute pain management) vs weight-based dosing in the ED and found that participants randomized into the patient-specific protocol had a greater reduction in pain and decreased rate of hospital admission.⁴

The panel acknowledges that intravenous patient-controlled opioid analgesia is generally the standard of care at most institutions. However, no clear data address whether continuous opioid infusion in addition to on-demand dosing is beneficial.

Recommendation 3. For adult and pediatric patients with acute pain related to SCD, the ASH guideline panel suggests a short course (5 to 7 days) of nonsteroidal anti-inflammatory drugs (NSAIDs) in addition to opioids (Conditional recommendation; very low certainty in the evidence about effects).

The use of NSAIDs for managing pain in hospitalized patients with SCD has been associated with a reduction in the use of opioids in the inpatient setting and decreased lengths of stay.⁵ The potential harms of NSAIDs, including renal and gastrointestinal toxicity, however, should be factored into the decision-making as the risks may outweigh the potential benefits.

Recommendation 4. For adult and pediatric patients with SCD hospitalized for acute pain, the ASH guideline panel suggests a subanesthetic (analgesic) infusion of ketamine as adjunctive treatment of pain refractory or not effectively treated with opioids alone (Conditional recommendation; very low certainty in the evidence about effects). The guideline panel also suggests regional anesthesia for localized pain refractory or not effectively treated with opioids alone (Conditional recommendation; very low certainty in the evidence about effects).

Studies have demonstrated reduced pain and opioid utilization in individuals who received adjuvant ketamine infusions⁶ or regional anesthesia (ie, epidural).⁷ Feasibility, however, is limited to centers that have the appropriate experience and expertise with these interventions.

Recommendation 5. For adult and pediatric patients who have recurrent acute pain associated with SCD, the ASH guideline panel suggests against chronic monthly transfusion therapy as a first-line strategy to prevent or reduce recurrent acute pain episodes (Conditional recommendation; low certainty in the evidence about effects). The evidence for monthly transfusions in preventing recurrent pain is limited. There is, however, a moderate risk of harm, including iron overload and transfusion reactions, in addition to substantial burden and costs.

Chronic Pain

Chronic pain in the guideline is defined as ongoing pain present on most days over the past 6 months.

Recommendation 6. For adult patients with SCD who have chronic pain from the SCD-related identifiable cause avascular necrosis (AVN) of the bone, the ASH guideline panel suggests the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) or NSAIDs in the context of a comprehensive disease and pain management plan (Conditional recommendation; very low certainty in the evidence about effects). For patients with no identifiable cause beyond SCD, the guideline panel suggests SNRIs, tricyclic antidepressants, or gabapentinoids for pain management (Conditional recommendation; very low certainty in the evidence about effects). Given the lack of direct evidence, indirect evidence was used to formulate these recommendations. For pain associated with AVN, data were extrapolated from literature on osteoarthritis, a form of degenerative arthropathy. For pain without an identifiable cause, evidence was taken from studies on fibromyalgia, a condition the panel felt most closely aligned with chronic pain related to SCD.

No recommendations were made for pediatric patients as the indirect evidence base only addressed adult patients.

Recommendation 7. For adult and pediatric patients with SCD and emerging and/or recently developed chronic pain, the ASH guideline panel does not recommend initiating COT unless pain is refractory to multiple other treatment modalities (Conditional recommendation; very low certainty in the evidence about effects). For patients receiving COT who are functioning well and have perceived benefit, the ASH guideline panel suggests shared decision-making for continuation of COT (Conditional recommendation; very low certainty in the evidence about effects).

High-quality data on the benefit of long-term COT in individuals with chronic noncancer pain are lacking. The panel maintains that the decision to initiate or continue COT should be individualized after weighing appropriate risks and benefits.

Recommendation 8. For adult and pediatric patients with chronic pain related to SCD, the panel suggests cognitive and behavioral pain management strategies in the context of a comprehensive disease and pain management plan (Conditional recommendation; very low certainty in the evidence about effects). Cognitive behavioral therapy may decrease overall pain intensity and improve coping skills.⁸ The panel agrees that medications alone may not be effective in reducing the burden of chronic pain in adult and pediatric patients with SCD.

The guidelines were created by a multidisciplinary panel that included physicians from hematology, pain medicine, psychiatry, and emergency medicine, a doctoral nurse practitioner, and two patient representatives. The Mayo Evidence-Based Practice Research Program supported the guideline-development process. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to assess evidence and make recommendations.

High-quality data in treating acute and chronic pain in both adult and pediatric patients with SCD are limited. As such, the majority of recommendations in these guidelines are conditional. The panel included studies that were indirectly related to SCD based on consensus (eg, inferred data from disease processes thought to be similar to SCD). One panelist disclosed receiving direct payments from a company that could be affected by these guidelines; however, it was deemed that the conflict was unlikely to have influenced any recommendations.

The panel acknowledges that further investigation is needed for both nonpharmacologic and pharmacologic modalities in treating acute and chronic pain related to SCD. Examples include evaluating the comparative-effectiveness of COT vs nonopioid pharmacotherapy, the benefits and harms of continuous opioid infusions in acute pain crises, and the impact of chronic transfusions on acute and chronic pain.

Sickle cell disease (SCD) affects an estimated 100,000 people in the United States.¹ Pain is the most common complication of SCD and the primary reason patients with SCD seek medical attention.² In 2016, three-fourths of the approximately 130,000 SCD-related hospitalizations in the United States involved pain crises.³ When managing patients with SCD and chronic pain, an individualized and interdisciplinary approach is crucial. In 2020, the American Society of Hematology (ASH) developed guidelines reflecting the latest evidence in managing acute and chronic pain in adult and pediatric patients with SCD. The ASH guidelines provide 18 recommendations; here, we highlight the 8 recommendations most pertinent to the hospitalist.

Acute Pain

Acute pain in the guideline is defined as pain that results in an unplanned visit to an acute care center for treatment.

Recommendation 1. For adult and pediatric patients presenting to an acute care setting with SCD-related acute pain, the ASH guideline panel recommends rapid (ie, within 1 hour of arrival at the emergency department [ED]) assessment and administration of analgesia, with reassessments every 30-60 minutes to optimize pain control (Strong recommendation; low certainty in the evidence about effects).

Although the perceived benefits are unclear due to insufficient evidence, the panel agrees that delaying pain management results in undeniable harm to patients. Hence, this recommendation was deemed both acceptable and ethical. Rapid evaluation also allows for earlier identification and treatment of other potential SCD-related complications.

Recommendation 2. For adult and pediatric patients presenting to an acute care setting with SCD-associated pain for whom opioid therapy is indicated, the ASH guideline panel suggests tailored opioid dosing based on consideration of baseline opioid therapy and prior effective therapy. (For adults: conditional recommendation; moderate certainty in the evidence about effects. For children: conditional recommendation; low certainty in the evidence about effects).

One randomized controlled trial examined patient-specific opioid dosing (based on current chronic opioid therapy [COT] and previously known effective acute pain management) vs weight-based dosing in the ED and found that participants randomized into the patient-specific protocol had a greater reduction in pain and decreased rate of hospital admission.⁴

The panel acknowledges that intravenous patient-controlled opioid analgesia is generally the standard of care at most institutions. However, no clear data address whether continuous opioid infusion in addition to on-demand dosing is beneficial.

Recommendation 3. For adult and pediatric patients with acute pain related to SCD, the ASH guideline panel suggests a short course (5 to 7 days) of nonsteroidal anti-inflammatory drugs (NSAIDs) in addition to opioids (Conditional recommendation; very low certainty in the evidence about effects).

The use of NSAIDs for managing pain in hospitalized patients with SCD has been associated with a reduction in the use of opioids in the inpatient setting and decreased lengths of stay.⁵ The potential harms of NSAIDs, including renal and gastrointestinal toxicity, however, should be factored into the decision-making as the risks may outweigh the potential benefits.

Recommendation 4. For adult and pediatric patients with SCD hospitalized for acute pain, the ASH guideline panel suggests a subanesthetic (analgesic) infusion of ketamine as adjunctive treatment of pain refractory or not effectively treated with opioids alone (Conditional recommendation; very low certainty in the evidence about effects). The guideline panel also suggests regional anesthesia for localized pain refractory or not effectively treated with opioids alone (Conditional recommendation; very low certainty in the evidence about effects).

Studies have demonstrated reduced pain and opioid utilization in individuals who received adjuvant ketamine infusions⁶ or regional anesthesia (ie, epidural).⁷ Feasibility, however, is limited to centers that have the appropriate experience and expertise with these interventions.

Recommendation 5. For adult and pediatric patients who have recurrent acute pain associated with SCD, the ASH guideline panel suggests against chronic monthly transfusion therapy as a first-line strategy to prevent or reduce recurrent acute pain episodes (Conditional recommendation; low certainty in the evidence about effects). The evidence for monthly transfusions in preventing recurrent pain is limited. There is, however, a moderate risk of harm, including iron overload and transfusion reactions, in addition to substantial burden and costs.

Chronic Pain

Chronic pain in the guideline is defined as ongoing pain present on most days over the past 6 months.

Recommendation 6. For adult patients with SCD who have chronic pain from the SCD-related identifiable cause avascular necrosis (AVN) of the bone, the ASH guideline panel suggests the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) or NSAIDs in the context of a comprehensive disease and pain management plan (Conditional recommendation; very low certainty in the evidence about effects). For patients with no identifiable cause beyond SCD, the guideline panel suggests SNRIs, tricyclic antidepressants, or gabapentinoids for pain management (Conditional recommendation; very low certainty in the evidence about effects). Given the lack of direct evidence, indirect evidence was used to formulate these recommendations. For pain associated with AVN, data were extrapolated from literature on osteoarthritis, a form of degenerative arthropathy. For pain without an identifiable cause, evidence was taken from studies on fibromyalgia, a condition the panel felt most closely aligned with chronic pain related to SCD.

No recommendations were made for pediatric patients as the indirect evidence base only addressed adult patients.

Recommendation 7. For adult and pediatric patients with SCD and emerging and/or recently developed chronic pain, the ASH guideline panel does not recommend initiating COT unless pain is refractory to multiple other treatment modalities (Conditional recommendation; very low certainty in the evidence about effects). For patients receiving COT who are functioning well and have perceived benefit, the ASH guideline panel suggests shared decision-making for continuation of COT (Conditional recommendation; very low certainty in the evidence about effects).

High-quality data on the benefit of long-term COT in individuals with chronic noncancer pain are lacking. The panel maintains that the decision to initiate or continue COT should be individualized after weighing appropriate risks and benefits.

Recommendation 8. For adult and pediatric patients with chronic pain related to SCD, the panel suggests cognitive and behavioral pain management strategies in the context of a comprehensive disease and pain management plan (Conditional recommendation; very low certainty in the evidence about effects). Cognitive behavioral therapy may decrease overall pain intensity and improve coping skills.⁸ The panel agrees that medications alone may not be effective in reducing the burden of chronic pain in adult and pediatric patients with SCD.

The guidelines were created by a multidisciplinary panel that included physicians from hematology, pain medicine, psychiatry, and emergency medicine, a doctoral nurse practitioner, and two patient representatives. The Mayo Evidence-Based Practice Research Program supported the guideline-development process. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to assess evidence and make recommendations.

High-quality data in treating acute and chronic pain in both adult and pediatric patients with SCD are limited. As such, the majority of recommendations in these guidelines are conditional. The panel included studies that were indirectly related to SCD based on consensus (eg, inferred data from disease processes thought to be similar to SCD). One panelist disclosed receiving direct payments from a company that could be affected by these guidelines; however, it was deemed that the conflict was unlikely to have influenced any recommendations.

The panel acknowledges that further investigation is needed for both nonpharmacologic and pharmacologic modalities in treating acute and chronic pain related to SCD. Examples include evaluating the comparative-effectiveness of COT vs nonopioid pharmacotherapy, the benefits and harms of continuous opioid infusions in acute pain crises, and the impact of chronic transfusions on acute and chronic pain.