Therapy insight: Prophylaxis of stress-induced gastrointestinal bleeding in critically ill patients

Stress-induced gastrointestinal bleeding is associated with increased morbidity and mortality in critically ill patients. Within the past few decades, the incidence of stress-induced gastrointestinal bleeding has decreased. Prophylaxis of stress-induced gastrointestinal bleeding, which is aimed at preventing morbidity and mortality, has to be achieved with as few adverse effects as possible. Data indicate that not all critically ill patients need prophylaxis for stress-induced gastrointestinal bleeding. The main risk factors associated with clinically important hemorrhage are mechanical ventilation for >48 h, and coagulopathy (thrombocyte count <50/nl, partial thromboplastin time (PTT) >2 times the upper limit of the normal range, international normalized ratio (INR) >1.5). Ranitidine is more effective than sucralfate for the prevention of clinically important bleeding. Immediate-release omeprazole is as effective as cimetidine, and is more efficient at increasing the intragastric pH. As yet, however, there is no firm evidence that any of the drugs used for prophylaxis of stress-induced gastrointestinal bleeding in critically ill patients decrease mortality or the length of hospital stay. When to stop prophylaxis is decided on clinical grounds rather than on the basis of data from clinical studies.     

Aggressive endoscopic hemostasis for severe gastrointestinal bleeding in critically ill patients to decrease mortality

BACKGROUND/AIMS: In critically ill patients, with gastrointestinal (GI) bleeding achieving endoscopic hemostasis has been reported to be often difficult, with a high rebleeding rate. The purpose of this study was to examine the efficacy of endoscopic hemoclipping for severe GI bleeding in critically ill patients. METHODOLOGY: This prospective study was performed at the Department of Traumatology and Critical Care Medicine, Kyorin University Hospital from June 1996 to December 1999. Patients with predefined clinically significant GI bleeding were treated using an established endoscopic hemoclipping protocol that covered indications and procedures. RESULTS: A total of 1429 patients were enrolled in this study. Of 11 hospitalized cases meeting the definition of severe GI bleeding, it occurred at 12.3 +/- 3.9 days (mean +/- SD) after admission. Initial hemostasis was possible in all patients. Although rebleeding was seen in 1 patient, the permanent hemostasis rate by additional endoscopic hemostasis was 100%. Of the 11, 9 patients were discharged and there were 2 hospital deaths. The direct cause of death depended on the degree of underlying critical illness and combined severe pneumonia. Complications caused by endoscopic hemostasis were not seen in any patient. CONCLUSIONS: Endoscopic hemostasis is useful in critically ill patients with the severe GI bleeding that occurs during critical care in the intensive care unit.     

Prevalence and risk factors of stress-induced gastrointestinal bleeding in critically ill children

AIM: To assess the frequency and the risk factors of stress-induced gastrointestinal (GI) bleeding in children admitted to a pediatric intensive care unit (PICU). METHODS: The medical records of children aged between 1 month and 15 years admitted to the PICU between January 2002 and December 2002 were reviewed. Demographic data, indications for PICU admission, principle diagnosis, and basic laboratory investigations were recorded. Previously described factors for stress ulcer bleeding (mechanical ventilation, sepsis, acute respiratory distress syndrome, renal insufficiency, coagulopathy, thrombocytopenia, and intracranial pathology) were used as independent variables in a multivariate analysis. RESULTS: One hundred and seventy of two hundred and five medical records were eligible for review. The most common indication for PICU admission was respiratory failure (48.8%). Twenty-five children received stress ulcer bleeding prophylaxis with ranitidine. The incidence of stress ulcer bleeding was 43.5%, in which 5.3% were clinically significant bleeding. Only mechanical ventilation and thrombocytopenia were significantly associated with stress ulcer bleeding using the univariate analysis. The odds ratio and 95% confidence intervals were 5.13 (1.86-14.12) and 2.26 (1.07-4.74), respectively. However, the logistic regression analysis showed that mechanical ventilation was the only significant risk factor with the odds ratio of 14.1. CONCLUSION: The incidence of gastrointestinal bleeding was high in critically ill children. Mechanical ventilation was an important risk factor for gastrointestinal bleeding.     

Clinically manifest gastrointestinal bleeding in patients subject to coronary angiography

PATIENT SET AND METHODOLOGY: The authors evaluated the incidence of acute bleeding from the upper gastrointestinal tract in 5,955 patients (of which 3,684 men and 2,271 women) during hospitalisation for coronary angiography, and the incidence of potential sources of bleeding from the upper gastrointestinal tract in the patients without bleeding. RESULTS: Bleeding occurred in 9 persons, within 3.4 +/- 3.6 days of the coronary angiography (the median of 1.0 day), with a 33% mortality rate. An ulcer of the duodenal bulbus or bulbitis were detected in four cases (44%), esophagitis in one case (11%), esophageal varices in one case, stomach carcinoma in one case, and the source of bleeding could not be detected in 2 cases. Patients with bleeding were significantly older than those without bleeding (73.6 +/- 4.4 years vs. 65.8 +/- 10.6 years, p < 0.001). Treatment with clopidogrel or abciximab was not associated with a higher incidence of bleeding (p > 0.05). In 42 patients without bleeding, the following pathologies were detected by gastroscopy: esophagitis (31%), mouth and stomach ulcers (36%), duodenal ulcers (21%), (12%), esophageal varices (2%) The incidence of mouth ulcers, stomach ulcers and duodenal ulcers was significantly higher in patients taking acetylsalicylic acid on a regular basis (p < 0.025). CONCLUSION: Bleeding from the upper gastrointestinal tract is not frequent shortly after coronary angiography, but the related mortality is high. The most frequent source of bleeding are duodenal peptic lesions most likely caused by previous treatment by acetylsalicylic acid.     

Early lactate clearance for predicting active bleeding in critically ill patients with acute upper gastrointestinal bleeding: a retrospective study

Not all patients with upper gastrointestinal bleeding (UGIB) require emergency endoscopy. Lactate clearance has been suggested as a parameter for predicting patient outcomes in various critical care settings. This study investigates whether lactate clearance can predict active bleeding in critically ill patients with UGIB. This single-center, retrospective, observational study included critically ill patients with UGIB who met all of the following criteria: admission to the emergency department (ED) from April 2011 to August 2014; had blood samples for lactate evaluation at least twice during the ED stay; and had emergency endoscopy within 6 h of ED presentation. The main outcome was active bleeding detected with emergency endoscopy. Classification and regression tree (CART) analyses were performed using variables associated with active bleeding to derive a prediction rule for active bleeding in critically ill UGIB patients. A total of 154 patients with UGIB were analyzed, and 31.2 % (48/154) had active bleeding. In the univariate analysis, lactate clearance was significantly lower in patients with active bleeding than in those without active bleeding (13 vs. 29 %, P < 0.001). Using the CART analysis, a prediction rule for active bleeding is derived, and includes three variables: lactate clearance; platelet count; and systolic blood pressure at ED presentation. The rule has 97.9 % (95 % CI 90.2–99.6 %) sensitivity with 32.1 % (28.6–32.9 %) specificity. Lactate clearance may be associated with active bleeding in critically ill patients with UGIB, and may be clinically useful as a component of a prediction rule for active bleeding.     

Risk factors for upper gastrointestinal rebleeding in critically ill patients

BACKGROUND/AIMS: To determine the risk factors for rebleeding after upper gastrointestinal bleeding in critically ill patients. METHODOLOGY: We retrospectively analyzed the medical records of consecutive 60 patients undergoing bedside esophagogastroduodenoscopy between January 2000 and December 2004 for upper gastrointestinal bleeding that developed while in the ICU. RESULTS: Eight of the 60 patients died within 7 days after initial bleeding and two of the eight died due to upper gastrointestinal bleeding. Seven-day rebleeding rate was 34.6% (18/52). An additional 7 patients died within 30 days, none of whom died of upper gastrointestinal bleeding. Thirty-day rebleeding rate was 51.1% (23/45). In multiple logistic regression using selected significant variables, anemia (Hb < 9.0g/dL), and hypoalbuminemia (albumin < 3.0g/dL) for 7-day rebleeding, and hypoxia (PaO2 < 80mmHg), anemia (Hb < 9.0g/dL), and units of blood transfused (> or = 3) for 30-day rebleeding were the significant independent risk factors in critically ill patients. CONCLUSIONS: The results of this study suggest that underlying patients' conditions or the severity of initial upper gastrointestinal bleeding affect rebleeding in the ICU setting. Adequate general ICU care including the prevention of initial bleeding and correction of hypoxia, anemia, and hypoalbuminemia after bleeding could reduce the rebleeding risk.     

Impacts and patterns of disturbed gastrointestinal function in critically ill patients

Disordered upper gastrointestinal tract motility occurs frequently in intensive care unit patients and often represents a substantial treatment challenge. In addition to specific complications such as pulmonary aspiration and diarrhea, abnormal gastrointestinal motility is a limiting factor for delivery and success of enteral nutrition. The pathophysiologies involved are incompletely understood because of the difficulties of making measurements of gastrointestinal function in critically ill patients. With the recent development of techniques that overcome some of these difficulties, the prospects are brighter for significant advances in this field.     

Stress ulcer prophylaxis in critically ill patients: a randomized controlled trial

BACKGROUND/AIMS: Critically ill patients especially who require mechanical ventilation or have coagulopathy are at increased risk for stress-related gastrointestinal hemorrhage. There are conflicting data on the efficacy and complication rates of various prophylactic regimens. METHODOLOGY: Our single-center randomized, placebo-controlled study included 287 patients with high risk for stress-related upper gastrointestinal hemorrhage (>48 h mechanical ventilation, coagulopathy). We compared 3 prophylactic regimens (proton pump inhibitor--omeprazole 40 mg i.v. once daily, n=72; H2 antagonists--famotidine 40 mg twice a day, n=71; and sucralfate 1 g every 6 hours, n=69) with placebo (n=75) in patients with trauma or after major surgery. RESULTS: Of 287 assessable patients, clinically significant stress-related upper gastrointestinal bleeding was observed in 1%, 3%, 4%, and 1% of patients assigned to receive omeprazole, famotidine, sucralfate, and placebo, respectively (p>0.28). Bleeding developed significantly more often in patients with coagulopathy compared with the others (10% vs. 2%; p=0.006). The gastric pH (p>0.001) and gastric colonization (p<0.05) was significantly higher in the patients who received pH increasing substances when compared with the other 2 groups. Nosocomial pneumonia occurred in 11% of patients receiving omeprazole, in 10% of famotidine patients, in 9% of sucralfate patients and in 7% of controls (p>0.34). No statistically significant differences were found for days on ventilator, length of ICU stay, or mortality among all the 4 groups. CONCLUSIONS: We could not show that omeprazole, famotidine, or sucralfate prophylaxis can affect already very low incidence of clinically important stress-related bleeding in high-risk surgical intensive care unit patients. Furthermore, our data suggested that especially gastric pH increasing medication could increase the risk for nosocomial pneumonia. Routine prophylaxis for stress-related bleeding even in high-risk patients seems not to be justified.     

Cimetidine prophylaxis for gastrointestinal bleeding in an intensive care unit.

The efficacy of cimetidine in the prevention of gastrointestinal haemorrhage in a general intensive care unit was evaluated in 221 patients by a placebo controlled double blind randomised study. Criteria for bleeding were (i) haematemesis or gastric aspirate greater than 50 ml fresh blood, (ii) melaena or fresh blood per rectum with an upper source verified by endoscopy if the gastric aspirate was clear, (iii) a fall in haemoglobin level greater than 2 g/dl in a 24 hour period associated with either 4+ occult blood in stools, or coffee ground gastric drainage of at least 100 ml. The drug and placebo groups were similar for age, sex, duration of study and risk factors. One hundred and fourteen received cimetidine and 107 placebo. Only 8% of the patients bled with no significant difference between the two groups (6/114 cimetidine, 11/107 placebo; p = 0.16). There was no correlation between the frequency of bleeding and either the number of risk factors per patient or the duration of intensive care unit stay. Thirteen patients died in each study group, resulting in overall mortality of 12%. The low incidence of haemorrhage, the lack of statistical benefit from cimetidine and the similar mortality all argue against the routine use of this drug in intensive care unit patients.     

Thrombocytopenia in critically ill patients

Critically ill patients often have a low platelet count. A proper identification of the underlying cause of this abnormality is required, because various underlying disorders may necessitate different diagnostic and therapeutic management strategies. Platelets are part of the first line of defense of the body against bleeding, hence, thrombocytopenia may increase the risk of hemorrhage. In case of systemic inflammatory syndromes, such as the response to sepsis, disseminated intravascular platelet activation may occur, which will contribute to microvascular failure and thereby play a role in the development of organ dysfunction. A low platelet count is a strong and independent predictor of an adverse outcome in critically ill patients, thereby facilitating a simple and practical risk assessment in these patients and potentially guiding the use of complex or expensive treatment strategies.     

Fibrinolysis in critically ill patients

Impaired fibrinolysis may contribute to development of adult respiratory distress syndrome (ARDS). Pathologic increases in endogenous plasminogen activator inhibitor (PAI-1) may blunt normal fibrinolysis and unmask alternate fibrinolytic mechanisms, such as elastase-induced fibrin degradation. We measured PAI-1 and elastase-induced fibrin(ogen) degradation products in 69 critically ill patients in our medical intensive care unit (MICU) and in nine healthy volunteers. Factor VIII-related antigen protein (VIII:Ag), a reported marker of acute lung injury, and alpha-1-protease inhibitor (alpha-1-PI), an acute phase reactant, were also measured. MICU patients included 24 control patients with no known risk of ARDS, 35 patients with risk factors for ARDS including sepsis, pneumonia, aspiration, and shock, and 12 patients with ARDS including two patients from at-risk groups who developed ARDS. Plasma PAI-1 was determined by chromogenic assay, elastase-induced peptides by a new radioimmunoassay, VIII:Ag by immunoelectrophoresis, and alpha-1-PI by immunodiffusion. When compared to normal volunteers, MICU control patients had elevated PAI-1, VIII:Ag, elastase-induced peptides, and alpha-1-PI. Patients with ARDS had significantly higher PAI-1 and VIII:Ag than did MICU control patients; elastase-induced peptides and alpha-1-PI were not higher. However, at-risk patients who did not develop ARDS also had high PAI-1 or VIII:Ag. Although these data cannot refute the possible role of these compounds in the pathogenesis of ARDS, they demonstrate that PAI-1 and VIII:Ag may be elevated in many critically ill patients but may not be useful markers for the subsequent development of ARDS.     

Anemia in critically ill patients

Anemia is common in acute critically ill patients. Although blood loss, either by trauma, surgery, phlebotomies or gastrointestinal bleeding, may play a role, the anemia in these patients bears many similarities to the anemia characteristic of chronic disease. Serum iron is low with a high concentration of ferritin and low-to-normal transferrin and serum transferrin receptor levels. Several mechanisms may be involved, with inflammation playing a crucial role. Although the exact nature of the inflammatory response and the role of various cytokines need further elucidation, it is known that inflammation blunts the responsiveness of the hormone erythropoietin and induces functional iron deficiency. Iron is trapped in cells of the mononuclear phagocytic system and its release is temporarily blocked. The bone marrow is still capable of incorporating iron and of responding to treatment with recombinant human erythropoietin (rh-EPO). The duration of the anemia is related to the persistence of the inflammation. Although the effects of anemia on morbidity and mortality in the critically ill are poorly defined, a restrictive transfusion policy, in which hemoglobin concentration is maintained between 7.0 and 9.0 g/dl, proves to be at least as effective as, if not superior to, a more liberal regimen. In individual situations, such as in cardiovascular and cancer patients, higher thresholds may be appropriate. The administration of rh-EPO is an alternative to reduce the need for red blood cell transfusions and to avoid transfusion-related complications. Although its efficacy has been shown, questions regarding cost-benefit, dose regimen and clinical outcomes need to be answered before its large-scale use can be recommended.     

Antibiotic-impregnated catheters associated with significant decrease in nosocomial and multidrug-resistant bacteremias in critically ill patients

OBJECTIVE: To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU. DESIGN: Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999). SETTING: ICUs of a tertiary care hospital in Houston, TX. PATIENTS: Cancer patients in the medical ICU (MICU) and surgical ICU (SICU). INTERVENTIONS: ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999. Measurements and main results:The rates of nosocomial BSIs and other patients' characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients' characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999. CONCLUSIONS: The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays.     

Nd:YAG laser in treatment of seriously ill patients with gastrointestinal bleeding

Nd:YAG (neodymium:yttrium aluminum garnet) laser coagulation was used to treat 30 seriously ill patients with massive or prolonged gastrointestinal bleeding. An average of 7.5 units of blood was given prior to Nd:YAG laser treatment. Twenty patients showed no evidence of continued or recurrent bleeding after laser therapy, four patients rebled after 48 hours, three patients rebled within 48 hours, one patient continued to bleed despite the laser treatment but died of an unrelated cause, one patient required immediate surgery because of inability to control bleeding, and one patient died several hours after control of the bleeding. Although six patients died within 10 weeks, no patient exsanguinated. Nd:YAG laser treatment is a useful modality for controlling severe gastrointestinal bleeding in the seriously ill patient.