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Prophylactic Endotracheal Intubation for Emergency Endoscopy in Critically Ill Patients?
April 2010
SELECTED SUMMARIES
notransferase, serum albumin, cirrhosis, and active viral hepatitis. Collectively, we think it is extremely unlikely that the observed silencing of miRNA-26 in HCC results from its induction in nontumor liver tissues owing to chronic viral hepatitis. With regard to the end point criteria used to evaluate the significance of miRNA-26, we think that overall survival, but not recurrence-free survival, is the best end point to evaluate the benefit of a treatment on HCC, because this result is more meaningful to patients. Moreover, in our retrospective analysis, the mortality of 87% of the HCC patients (n ⫽ 2,160) was directly attributed to postoperative tumor recurrence (unpublished data), suggesting a minimal impact, if any, of liver failure to overall survival. We agree with Drs Boix and Bruix’s viewpoint that the characteristics of the tumor are still the most important factor affecting patient survival. We agree that there is an urgent need to develop molecular diagnostic tools by profiling tumor specimens to assist clinical staging and accurately select patients for appropriate courses of treatment. The implementation of such a strategy in clinical practice is crucial to reduce tumor burden and improve patient outcomes. XIN WEI WANG, PHD JUNFANG JI, PHD ANURADHA BUDHU, PHD Liver Carcinogenesis Section Laboratory of Human Carcinogenesis Center for Cancer Research National Cancer Institute Bethesda, Maryland HUI–CHUAN SUN, MD, PHD Liver Cancer Institute and Zhongshan Hospital Fudan University Shanghai, China
PROPHYLACTIC ENDOTRACHEAL INTUBATION FOR EMERGENCY ENDOSCOPY IN CRITICALLY ILL PATIENTS? Rehman A, Iscimen R, Yilmaz M, et al. (Division of Pulmonary and Critical Care Medicine, Rochester, Minnesota; Bursa, Antalya, Turkey). Prophylactic endotracheal intubation in critically ill patients undergoing endoscopy for upper GI hemorrhage. Gastrointest Endosc 2009;69:e55–59. Endoscopy for upper gastrointestinal (GI) bleeding in the intensive care unit (ICU) is a demanding procedure. There are several recommendation about management, medical, and endoscopic treatment of these emergency situations (Gastrointest Endosc 2004;60:497–504; Gastrointest Endosc 2005;62:651– 655; Gut 2002;51:1– 6). Aspiration and cardiopulmonary complications are the most serious and life-threatening complications of such
1627
interventions, occurring in up to 20% of cases (Crit Care Med 1991;19:330 –333). In some guidelines or standardized operating procedures of endoscopic units, prophylactic endotracheal intubation is recommended for severe upper GI bleeding to prevent these potential complications (Gut 2002;51:1– 6). It is also unclear whether critically ill patients should receive prophylactic intubation for diagnostic or therapeutic upper GI endoscopies. Rehman et al (Gastrointest Endosc 2009;69:55–59) conducted a retrospective, propensity-matched, case-control study of the clinical benefit of prophylactic endotracheal intubation before endoscopy in patients admitted to the ICU because of upper GI bleeding. In a tertiary center (The Mayo Clinic), all high-risk patients admitted for complicated upper GI bleeding (presence of cirrhosis, hematemesis, shock) who underwent endoscopy for upper GI hemorrhage were identified. Patients not willing to participate, intubated for other reasons, or intubated before admission to the ICU were excluded. All patients received conscious sedation for upper GI endoscopy, and patients intubated for airway protection before upper GI endoscopy were identified. Using univariate and multivariate logistic regression, risk factors for intubation (age, Acute Physiology and Chronic Health Evaluation III score, hematemesis, number of transfusions, preexisting lung disease) were identified. Using these risk factors in a propensity analysis, cases intubated were matched with nonintubated patients with similar probability and severity. The primary outcome measurements of the study were the cumulative incidence of cardiopulmonary complications, myocardial infarction or cardiac arrest within 12 hours, the rate of aspiration pneumonia, acute respiratory distress syndrome, or cardiogenic pulmonary edema, ICU and hospital length of stay, and mortality. Over a 54-month period, 487 patients were admitted; of these, 161 did not meet the inclusion criteria (presence of shock, hematemesis, or cirrhosis), 19 were intubated before entering the ICU or for other reasons, or were denied participation. Of the remaining 307 patients, 53 underwent elective prophylactic intubation before upper GI endoscopy. The probability of intubation was related to the Acute Physiology and Chronic Health Evaluation III score (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2–1.6), age (OR, 0.97; 95% CI, 0.95– 0.09), the presence of hematemesis (OR, 1.9; 95% CI, 0.8 –5.1), previous lung disease (OR, 2.1; 95% CI, 0.8 – 4.9), and the number of transfusions (OR, 1.1; 95% CI, 1.0 –1.1 per unit). Nonintubated, matched controls were identified for all but 4 patients with active massive hematemesis, who were excluded from matched analysis. Endoscopic interventions were performed in 17 controls (35%) versus 18 cases (37%) with no significant differences in the identified bleeding causes. Cumulative incidence of cardiopulmonary complications (53% vs 43%; P ⫽ NS), ICU duration of stay (median, 2.2 vs 1.8 days), and hospital length of
1628
SELECTED SUMMARIES
stay (6.9 vs 5.9 days), as well as hospital mortality (14% vs 20%) were similar. Especially the rate of aspiration (intubated vs non-intubated, 20% vs 18%), acute respiratory distress syndrome (16% vs 8%), pneumonia (18% vs 10%), and pulmonary edema (31% vs 16%) showed not even a numerical trend favoring intubation. Comment. GI bleeding is an emergency situation and diagnostic as well as therapeutic management has to be carefully planned. The study by Rehman et al demonstrates that GI endoscopy for suspected upper GI bleeding can be safely performed with conscious sedation in critically ill patients in an ICU setting. The rate of prophylactic intubation is relatively low (17.3%). Only 4 patients (1.3%) with massive hematemesis were excluded from the matched analysis. However, in most patients the prophylactic airway protection does not necessarily impact favorably on the clinical outcome. Airway protection with endotracheal intubation was not associated with decreased cardiopulmonary complication rates, or reduced length of stay in the ICU or the clinic. In the pre-endoscopic management era, there were specific independent risk factors and patient-specific factors favoring prophylactic intubation, such as severe underlying disease (especially pulmonary disease), but also by higher bleeding activity. However, even in these high-risk patients endotracheal intubation seems not to prevent complications; endoscopy can be performed with a similar outcome without intubation or mechanical ventilation. Most interestingly, intubation did not decrease the pulmonary complications, and there was not even a trend for this. These relatively surprising results confirm similar findings in patients undergoing emergency endoscopy for upper GI bleeding. Another study on the management upper GI bleedings compared emergency endoscopies without (intubation rate, 3%; n ⫽ 101) and with (intubation rate, 15.1%; n ⫽ 119) prophylactic intubation in 2 subsequent time periods. In this study, there was no significant difference in cardiopulmonary complications, new pulmonary infiltrates after upper GI, number of ICU days, and mortality (Gastrointest Endosc 2003;57:58 – 61). However, in the period with increased intubation rate there were no fatal episodes of aspiration, no post-EGD intubation requirements, and fewer in hospital cardiopulmonary arrests. Thus, there could be some long-term effect, although there is no clear, acute, protective effect of airway protection by prophylactic intubation. Thus, it seems that intubation will not decrease aspiration risk. There is evidence that even more aspirations and cardiopulmonary events might occur after intubation. In patients with severe variceal bleeding (n ⫽ 62), elective intubation was associated with even a higher risk of pulmonary infiltrates (17%) and higher mortality when compared with a group (n ⫽ 20) that was not intubated. It was concluded that intubation in patients with sus-
GASTROENTEROLOGY Vol. 138, No. 4
pected variceal bleeding is associated with a substantial risk of aspiration pneumonia (Dig Dis Sci 2007;52:2225– 2228). However, selection bias could have influenced these results. There are some case reports, especially in patients with esophageal varices, where severe bleeding episodes were induced by endotracheal intubation (J Emerg Med 2000;18:317–322). In most studies, the technique and mode of intubation are not clearly stated. Many ICUs are managed by anesthetists; in some countries, GI emergencies are cared for in internal medicine or gastroenterologic ICUs. Whether profession or background of the intensivist or mode of intubation (planned prophylactic vs emergency, fiber-optic guided) has any influence on the outcome is unclear. The most important and intriguing question whether emergency endoscopy for upper GI bleeding should be performed with prophylactic intubation cannot be conclusively answered from the study by Rehman et al. First, 4 patients with severe upper GI bleeding were excluded from further analysis, most likely because no matched controls could be found. However, a clear reason for this is not stated. Second, the bleeding activity in most of the patients was relatively minor; only 35% and 37% of the patients received an endoscopy intervention. Unfortunately, the bleeding activities and severity were not explicitly stated in this study. However, there exist past studies that also suggested that severe upper GI bleeding from esophageal varices would not benefit from an endotracheal intubation (Dig Dis Sci 2007;52:2225–2228). Intubation of a patient with severe upper GI bleeding is a technically demanding, high-risk procedure. The patient has to be sedated relatively deeply for intubation with loss of protective reflexes. Endoscopy, on the other hand, is often performed with mild conscious sedation and the possibility of suction and at least partial blockage of the esophagus. Early endoscopy and immediate hemostasis could therefore help to reduce the risk of aspiration. There is good evidence that timing and quality of the endoscopy are of major importance. Early EGD in upper GI bleeding was associated with significant severity-adjusted reduction in hospital and ICU stay. Appropriate intervention at initial EGD was associated with reductions in severity-adjusted length of ICU stay and rate of recurrent bleeding (Gastrointest Endosc 2001;53: 6 –13). In most endoscopic centers with an emergency endoscopy service, severe upper GI bleeds are usually referred to the ICU and the emergency endoscopy is performed after resuscitation and stabilization of the cardiopulmonary circulation. In cases with severe bleeding activity, endoscopy is performed in the ICU with ongoing transfusion and pharmacologic interventions. In most of these cases, the intubation is technically demanding and associated with a high risk for aspiration. Intubation of critically ill patients without upper GI bleeding is associated with a high risk for complications— up to 39%—and a risk for
April 2010
aspiration of 5.9% (Intens Care Med 2008;34:1835–1842; Crit Care Med 2006;34:2355–2361). On the other hand, when intubation has been performed the patient can be subjected to controlled ventilation, and the tracheal system can be inspected and cleared of potentially aspirated blood. In some situations, however, such as esophageal variceal bleeding or spurting bleeding from a gastric or duodenal ulcer, endoscopic intervention, such as placement of a ligation or a hemoclip, can lead to immediate and permanent hemostasis, reducing the risk cardiocirculatory depression and ongoing hematemesis. Additionally, in an acute bleeding situation, fresh blood can usually be removed easily and sucked with the endoscope, reducing the risk for aspiration. It is not clear whether aspiration of blood has similar negative outcomes as aspiration of gastric contents or acid, but massive aspiration can lead to fatal outcomes and respiratory failures. Intubation and intensive care managements could delay the possible therapeutic act.
SELECTED SUMMARIES
1629
The study by Rehman et al, together with earlier studies, questions the general benefit of prophylactic intubation. In most guidelines the management of severe upper GI bleeding is not stated in detail. Some guidelines state that consideration should be given to endotracheal intubation in severe bleeding to prevent pulmonary aspiration (Gut 2002:51;1– 6), whereas others give no statements. Given the importance of this intervention the data available on this topic are relatively sparse, and we should place more scientific interest in the benefit, need, and improvement of airway protection during emergency endoscopy. In general, the benefit and protective effect of intubation during emergency endoscopy for bleeding seems to be less evident than anticipated. HANS–DIETER ALLESCHER, MD Center for Internal Medicine Klinikum Garmisch-Partenkirchen Garmisch-Partenkirchen, Germany
SELECTED SUMMARIES
notransferase, serum albumin, cirrhosis, and active viral hepatitis. Collectively, we think it is extremely unlikely that the observed silencing of miRNA-26 in HCC results from its induction in nontumor liver tissues owing to chronic viral hepatitis. With regard to the end point criteria used to evaluate the significance of miRNA-26, we think that overall survival, but not recurrence-free survival, is the best end point to evaluate the benefit of a treatment on HCC, because this result is more meaningful to patients. Moreover, in our retrospective analysis, the mortality of 87% of the HCC patients (n ⫽ 2,160) was directly attributed to postoperative tumor recurrence (unpublished data), suggesting a minimal impact, if any, of liver failure to overall survival. We agree with Drs Boix and Bruix’s viewpoint that the characteristics of the tumor are still the most important factor affecting patient survival. We agree that there is an urgent need to develop molecular diagnostic tools by profiling tumor specimens to assist clinical staging and accurately select patients for appropriate courses of treatment. The implementation of such a strategy in clinical practice is crucial to reduce tumor burden and improve patient outcomes. XIN WEI WANG, PHD JUNFANG JI, PHD ANURADHA BUDHU, PHD Liver Carcinogenesis Section Laboratory of Human Carcinogenesis Center for Cancer Research National Cancer Institute Bethesda, Maryland HUI–CHUAN SUN, MD, PHD Liver Cancer Institute and Zhongshan Hospital Fudan University Shanghai, China
PROPHYLACTIC ENDOTRACHEAL INTUBATION FOR EMERGENCY ENDOSCOPY IN CRITICALLY ILL PATIENTS? Rehman A, Iscimen R, Yilmaz M, et al. (Division of Pulmonary and Critical Care Medicine, Rochester, Minnesota; Bursa, Antalya, Turkey). Prophylactic endotracheal intubation in critically ill patients undergoing endoscopy for upper GI hemorrhage. Gastrointest Endosc 2009;69:e55–59. Endoscopy for upper gastrointestinal (GI) bleeding in the intensive care unit (ICU) is a demanding procedure. There are several recommendation about management, medical, and endoscopic treatment of these emergency situations (Gastrointest Endosc 2004;60:497–504; Gastrointest Endosc 2005;62:651– 655; Gut 2002;51:1– 6). Aspiration and cardiopulmonary complications are the most serious and life-threatening complications of such
1627
interventions, occurring in up to 20% of cases (Crit Care Med 1991;19:330 –333). In some guidelines or standardized operating procedures of endoscopic units, prophylactic endotracheal intubation is recommended for severe upper GI bleeding to prevent these potential complications (Gut 2002;51:1– 6). It is also unclear whether critically ill patients should receive prophylactic intubation for diagnostic or therapeutic upper GI endoscopies. Rehman et al (Gastrointest Endosc 2009;69:55–59) conducted a retrospective, propensity-matched, case-control study of the clinical benefit of prophylactic endotracheal intubation before endoscopy in patients admitted to the ICU because of upper GI bleeding. In a tertiary center (The Mayo Clinic), all high-risk patients admitted for complicated upper GI bleeding (presence of cirrhosis, hematemesis, shock) who underwent endoscopy for upper GI hemorrhage were identified. Patients not willing to participate, intubated for other reasons, or intubated before admission to the ICU were excluded. All patients received conscious sedation for upper GI endoscopy, and patients intubated for airway protection before upper GI endoscopy were identified. Using univariate and multivariate logistic regression, risk factors for intubation (age, Acute Physiology and Chronic Health Evaluation III score, hematemesis, number of transfusions, preexisting lung disease) were identified. Using these risk factors in a propensity analysis, cases intubated were matched with nonintubated patients with similar probability and severity. The primary outcome measurements of the study were the cumulative incidence of cardiopulmonary complications, myocardial infarction or cardiac arrest within 12 hours, the rate of aspiration pneumonia, acute respiratory distress syndrome, or cardiogenic pulmonary edema, ICU and hospital length of stay, and mortality. Over a 54-month period, 487 patients were admitted; of these, 161 did not meet the inclusion criteria (presence of shock, hematemesis, or cirrhosis), 19 were intubated before entering the ICU or for other reasons, or were denied participation. Of the remaining 307 patients, 53 underwent elective prophylactic intubation before upper GI endoscopy. The probability of intubation was related to the Acute Physiology and Chronic Health Evaluation III score (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2–1.6), age (OR, 0.97; 95% CI, 0.95– 0.09), the presence of hematemesis (OR, 1.9; 95% CI, 0.8 –5.1), previous lung disease (OR, 2.1; 95% CI, 0.8 – 4.9), and the number of transfusions (OR, 1.1; 95% CI, 1.0 –1.1 per unit). Nonintubated, matched controls were identified for all but 4 patients with active massive hematemesis, who were excluded from matched analysis. Endoscopic interventions were performed in 17 controls (35%) versus 18 cases (37%) with no significant differences in the identified bleeding causes. Cumulative incidence of cardiopulmonary complications (53% vs 43%; P ⫽ NS), ICU duration of stay (median, 2.2 vs 1.8 days), and hospital length of
1628
SELECTED SUMMARIES
stay (6.9 vs 5.9 days), as well as hospital mortality (14% vs 20%) were similar. Especially the rate of aspiration (intubated vs non-intubated, 20% vs 18%), acute respiratory distress syndrome (16% vs 8%), pneumonia (18% vs 10%), and pulmonary edema (31% vs 16%) showed not even a numerical trend favoring intubation. Comment. GI bleeding is an emergency situation and diagnostic as well as therapeutic management has to be carefully planned. The study by Rehman et al demonstrates that GI endoscopy for suspected upper GI bleeding can be safely performed with conscious sedation in critically ill patients in an ICU setting. The rate of prophylactic intubation is relatively low (17.3%). Only 4 patients (1.3%) with massive hematemesis were excluded from the matched analysis. However, in most patients the prophylactic airway protection does not necessarily impact favorably on the clinical outcome. Airway protection with endotracheal intubation was not associated with decreased cardiopulmonary complication rates, or reduced length of stay in the ICU or the clinic. In the pre-endoscopic management era, there were specific independent risk factors and patient-specific factors favoring prophylactic intubation, such as severe underlying disease (especially pulmonary disease), but also by higher bleeding activity. However, even in these high-risk patients endotracheal intubation seems not to prevent complications; endoscopy can be performed with a similar outcome without intubation or mechanical ventilation. Most interestingly, intubation did not decrease the pulmonary complications, and there was not even a trend for this. These relatively surprising results confirm similar findings in patients undergoing emergency endoscopy for upper GI bleeding. Another study on the management upper GI bleedings compared emergency endoscopies without (intubation rate, 3%; n ⫽ 101) and with (intubation rate, 15.1%; n ⫽ 119) prophylactic intubation in 2 subsequent time periods. In this study, there was no significant difference in cardiopulmonary complications, new pulmonary infiltrates after upper GI, number of ICU days, and mortality (Gastrointest Endosc 2003;57:58 – 61). However, in the period with increased intubation rate there were no fatal episodes of aspiration, no post-EGD intubation requirements, and fewer in hospital cardiopulmonary arrests. Thus, there could be some long-term effect, although there is no clear, acute, protective effect of airway protection by prophylactic intubation. Thus, it seems that intubation will not decrease aspiration risk. There is evidence that even more aspirations and cardiopulmonary events might occur after intubation. In patients with severe variceal bleeding (n ⫽ 62), elective intubation was associated with even a higher risk of pulmonary infiltrates (17%) and higher mortality when compared with a group (n ⫽ 20) that was not intubated. It was concluded that intubation in patients with sus-
GASTROENTEROLOGY Vol. 138, No. 4
pected variceal bleeding is associated with a substantial risk of aspiration pneumonia (Dig Dis Sci 2007;52:2225– 2228). However, selection bias could have influenced these results. There are some case reports, especially in patients with esophageal varices, where severe bleeding episodes were induced by endotracheal intubation (J Emerg Med 2000;18:317–322). In most studies, the technique and mode of intubation are not clearly stated. Many ICUs are managed by anesthetists; in some countries, GI emergencies are cared for in internal medicine or gastroenterologic ICUs. Whether profession or background of the intensivist or mode of intubation (planned prophylactic vs emergency, fiber-optic guided) has any influence on the outcome is unclear. The most important and intriguing question whether emergency endoscopy for upper GI bleeding should be performed with prophylactic intubation cannot be conclusively answered from the study by Rehman et al. First, 4 patients with severe upper GI bleeding were excluded from further analysis, most likely because no matched controls could be found. However, a clear reason for this is not stated. Second, the bleeding activity in most of the patients was relatively minor; only 35% and 37% of the patients received an endoscopy intervention. Unfortunately, the bleeding activities and severity were not explicitly stated in this study. However, there exist past studies that also suggested that severe upper GI bleeding from esophageal varices would not benefit from an endotracheal intubation (Dig Dis Sci 2007;52:2225–2228). Intubation of a patient with severe upper GI bleeding is a technically demanding, high-risk procedure. The patient has to be sedated relatively deeply for intubation with loss of protective reflexes. Endoscopy, on the other hand, is often performed with mild conscious sedation and the possibility of suction and at least partial blockage of the esophagus. Early endoscopy and immediate hemostasis could therefore help to reduce the risk of aspiration. There is good evidence that timing and quality of the endoscopy are of major importance. Early EGD in upper GI bleeding was associated with significant severity-adjusted reduction in hospital and ICU stay. Appropriate intervention at initial EGD was associated with reductions in severity-adjusted length of ICU stay and rate of recurrent bleeding (Gastrointest Endosc 2001;53: 6 –13). In most endoscopic centers with an emergency endoscopy service, severe upper GI bleeds are usually referred to the ICU and the emergency endoscopy is performed after resuscitation and stabilization of the cardiopulmonary circulation. In cases with severe bleeding activity, endoscopy is performed in the ICU with ongoing transfusion and pharmacologic interventions. In most of these cases, the intubation is technically demanding and associated with a high risk for aspiration. Intubation of critically ill patients without upper GI bleeding is associated with a high risk for complications— up to 39%—and a risk for
April 2010
aspiration of 5.9% (Intens Care Med 2008;34:1835–1842; Crit Care Med 2006;34:2355–2361). On the other hand, when intubation has been performed the patient can be subjected to controlled ventilation, and the tracheal system can be inspected and cleared of potentially aspirated blood. In some situations, however, such as esophageal variceal bleeding or spurting bleeding from a gastric or duodenal ulcer, endoscopic intervention, such as placement of a ligation or a hemoclip, can lead to immediate and permanent hemostasis, reducing the risk cardiocirculatory depression and ongoing hematemesis. Additionally, in an acute bleeding situation, fresh blood can usually be removed easily and sucked with the endoscope, reducing the risk for aspiration. It is not clear whether aspiration of blood has similar negative outcomes as aspiration of gastric contents or acid, but massive aspiration can lead to fatal outcomes and respiratory failures. Intubation and intensive care managements could delay the possible therapeutic act.
SELECTED SUMMARIES
1629
The study by Rehman et al, together with earlier studies, questions the general benefit of prophylactic intubation. In most guidelines the management of severe upper GI bleeding is not stated in detail. Some guidelines state that consideration should be given to endotracheal intubation in severe bleeding to prevent pulmonary aspiration (Gut 2002:51;1– 6), whereas others give no statements. Given the importance of this intervention the data available on this topic are relatively sparse, and we should place more scientific interest in the benefit, need, and improvement of airway protection during emergency endoscopy. In general, the benefit and protective effect of intubation during emergency endoscopy for bleeding seems to be less evident than anticipated. HANS–DIETER ALLESCHER, MD Center for Internal Medicine Klinikum Garmisch-Partenkirchen Garmisch-Partenkirchen, Germany