Gastric Acid Suppressant Prophylaxis in Pediatric ICU
Gastric Acid Suppressant Prophylaxis in Pediatric ICU
Observations of stress-related gastrointestinal bleeding and the impact of H2 and PPIs on reducing gastric pH have established the practice of acid prophylaxis in PICU populations since the 1990s. Although the overall use of acid suppressant medications in children has increased 10-fold in the last decade, current use of these medications for stress-ulcer prophylaxis in the PICU populations is unknown. We examined current use of H2 and PPI in the PICU population as reflected in a large administrative database of U.S. children's hospitals. We limited our sample to direct admissions to the PICU and defined exposure as receiving these medications on the first hospital day in order to focus on prophylactic use of these agents. We observed that acid suppressants were used in the majority of patients and were continued through most of the PICU stay and half of the total hospitalization. While H2 were more frequently used, increasingly, a PPI is prescribed. Increasing PPI use was associated with the overall increase in prophylactic acid suppression over the study period. These findings are similar to observations from surveys of adult practice in the United States and United Kingdom. Consistent with past observations of the risk of stress-related bleeding in children, we did not find clinically important differences in age, gender, and race between those exposed to the medications and the unexposed.
Recently, the importance of gastric acid in host defense and nutrient absorption has been better appreciated, raising concerns that widespread use of these agents may contribute to infection and other complications. Given the limitations of the administrative database, we could not examine if any association with sepsis and pneumonia was secondary to the use of these agents. However, our observation that only a very small proportion of patients are diagnosed with gastrointestinal hemorrhage is consistent with a reduction in the prevalence of this complication in pediatric intensive care.
In this study, we found that prophylactic acid suppressants were used in a broad and diverse group of diseases but in patients with several of the most prevalent diagnoses use varied significantly from the population average. More frequent prophylaxis use occurred in children with acute respiratory failure, in asthma, when mechanical ventilation was needed, in patients needing surgery for congenital heart disease, in those with sepsis, and in children with a coagulopathy. The presence of a CCC was also associated with higher levels of use. Again, these findings are consistent with past determinations of risk factors for stress-related hemorrhage in adults and children.
Alternatively, some of the common PICU conditions were associated with less than average use of prophylaxis. These included children with diabetic ketoacidosis and those receiving surgical management of craniofacial abnormalities and surgery for scoliosis and those with status epilepticus. These observations were surprising because past studies of critically ill children have indicated that ketoacidosis, metabolic acidosis, prolonged surgery, and neurologic failure are risk factors for gastrointestinal hemorrhage. We were similarly surprised, given past recommendations, that head trauma, severely burned patients, and infants hospitalized in the PICU for treatment of viral bronchiolitis had less than average use. For the burn patients, the small number of hospitalizations may indicate that our sample does not reflect current practice. CCCs, particularly those associated with respiratory disease and neonatal disease, were associated with the use of these medications.
We observed dramatic regional-level and hospital-level associated variation in acid suppressant prophylaxis. When adjusted for the hospital effect, regional variation was less significant. Our multivariate explanatory model confirmed our observations of the importance of acute and chronic disease and treating hospital in current practice relating acid suppressant use in the PICU.
As noted above, gastrointestinal bleeding, the primary condition for which these medications are advocated, was recorded as a principal or additional diagnosis in a very small number of patients. Furthermore, children diagnosed with gastrointestinal hemorrhage who also received a transfusion included less than one half of 1% of the sample. Our findings are in contrast to earlier studies of the risk of bleeding in children but consistent with more recent observations in adults. We did observe an increased prevalence of gastrointestinal hemorrhage when we compared those with a principal diagnosis associated with frequent prescription of prophylactic acid suppressants with those with diagnoses associated with less frequent use of these medications. This observation may indicate that the prescription of prophylactic acid suppressants in PICU patients reflects clinical appreciation that some common diagnoses that lead to PICU admission are more frequently associated with gastrointestinal bleeding (i.e., residual confounding by indication). Nevertheless, our findings suggest that clinically important gastrointestinal hemorrhage, in the most recent era, is uncommon in the PICU population, even among patients with higher risk disease processes.
Our study has several limitations that warrant discussion. By using ICD-9 coding to identify diseases and treatments, we may have underestimated the prevalence of some health conditions. The PHIS dataset available for this study does not include clinical variables such as vital signs, laboratory and imaging studies or clinical scores, such as Glasgow coma score, therefore we could not use stratification or other adjustment techniques to better understand out findings. Similarly, information on prior home administration of acid suppressant medications was unavailable. As with any observational study, treatment with these agents was nonrandomized; therefore, indications for treatment and severity of illness may have biased our observed associations. Additionally, the timing of outcomes of interest to determine the sequence of events was not impossible; therefore, an outcome event could have occurred prior to exposure effect, invalidating any speculation regarding causality. As a result of these limitations, we were not able to examine important outcomes, such as mortality, length of stay, or infectious complications, in relation to acid suppressant exposure in this cohort.
In conclusion, we examined recent prophylactic gastric acid–suppressant medication use in a PICU population. We found that these medications are prescribed in most patients and are increasing over time, particularly the use of PPI medications. Significant variation exists in the use of these medications that is associated with acute and chronic diagnoses, treatment with mechanical ventilation, and treatment hospital. Provider preference is a likely source for some of the observed variation. Gastrointestinal hemorrhage is rare in the current era. Limitations inherent in the study design prevent examination of causation of outcomes with acid suppressant exposure. Future investigations seem warranted to reexamine the value and adverse effects of these medications in PICU patients.
Discussion
Observations of stress-related gastrointestinal bleeding and the impact of H2 and PPIs on reducing gastric pH have established the practice of acid prophylaxis in PICU populations since the 1990s. Although the overall use of acid suppressant medications in children has increased 10-fold in the last decade, current use of these medications for stress-ulcer prophylaxis in the PICU populations is unknown. We examined current use of H2 and PPI in the PICU population as reflected in a large administrative database of U.S. children's hospitals. We limited our sample to direct admissions to the PICU and defined exposure as receiving these medications on the first hospital day in order to focus on prophylactic use of these agents. We observed that acid suppressants were used in the majority of patients and were continued through most of the PICU stay and half of the total hospitalization. While H2 were more frequently used, increasingly, a PPI is prescribed. Increasing PPI use was associated with the overall increase in prophylactic acid suppression over the study period. These findings are similar to observations from surveys of adult practice in the United States and United Kingdom. Consistent with past observations of the risk of stress-related bleeding in children, we did not find clinically important differences in age, gender, and race between those exposed to the medications and the unexposed.
Recently, the importance of gastric acid in host defense and nutrient absorption has been better appreciated, raising concerns that widespread use of these agents may contribute to infection and other complications. Given the limitations of the administrative database, we could not examine if any association with sepsis and pneumonia was secondary to the use of these agents. However, our observation that only a very small proportion of patients are diagnosed with gastrointestinal hemorrhage is consistent with a reduction in the prevalence of this complication in pediatric intensive care.
In this study, we found that prophylactic acid suppressants were used in a broad and diverse group of diseases but in patients with several of the most prevalent diagnoses use varied significantly from the population average. More frequent prophylaxis use occurred in children with acute respiratory failure, in asthma, when mechanical ventilation was needed, in patients needing surgery for congenital heart disease, in those with sepsis, and in children with a coagulopathy. The presence of a CCC was also associated with higher levels of use. Again, these findings are consistent with past determinations of risk factors for stress-related hemorrhage in adults and children.
Alternatively, some of the common PICU conditions were associated with less than average use of prophylaxis. These included children with diabetic ketoacidosis and those receiving surgical management of craniofacial abnormalities and surgery for scoliosis and those with status epilepticus. These observations were surprising because past studies of critically ill children have indicated that ketoacidosis, metabolic acidosis, prolonged surgery, and neurologic failure are risk factors for gastrointestinal hemorrhage. We were similarly surprised, given past recommendations, that head trauma, severely burned patients, and infants hospitalized in the PICU for treatment of viral bronchiolitis had less than average use. For the burn patients, the small number of hospitalizations may indicate that our sample does not reflect current practice. CCCs, particularly those associated with respiratory disease and neonatal disease, were associated with the use of these medications.
We observed dramatic regional-level and hospital-level associated variation in acid suppressant prophylaxis. When adjusted for the hospital effect, regional variation was less significant. Our multivariate explanatory model confirmed our observations of the importance of acute and chronic disease and treating hospital in current practice relating acid suppressant use in the PICU.
As noted above, gastrointestinal bleeding, the primary condition for which these medications are advocated, was recorded as a principal or additional diagnosis in a very small number of patients. Furthermore, children diagnosed with gastrointestinal hemorrhage who also received a transfusion included less than one half of 1% of the sample. Our findings are in contrast to earlier studies of the risk of bleeding in children but consistent with more recent observations in adults. We did observe an increased prevalence of gastrointestinal hemorrhage when we compared those with a principal diagnosis associated with frequent prescription of prophylactic acid suppressants with those with diagnoses associated with less frequent use of these medications. This observation may indicate that the prescription of prophylactic acid suppressants in PICU patients reflects clinical appreciation that some common diagnoses that lead to PICU admission are more frequently associated with gastrointestinal bleeding (i.e., residual confounding by indication). Nevertheless, our findings suggest that clinically important gastrointestinal hemorrhage, in the most recent era, is uncommon in the PICU population, even among patients with higher risk disease processes.
Our study has several limitations that warrant discussion. By using ICD-9 coding to identify diseases and treatments, we may have underestimated the prevalence of some health conditions. The PHIS dataset available for this study does not include clinical variables such as vital signs, laboratory and imaging studies or clinical scores, such as Glasgow coma score, therefore we could not use stratification or other adjustment techniques to better understand out findings. Similarly, information on prior home administration of acid suppressant medications was unavailable. As with any observational study, treatment with these agents was nonrandomized; therefore, indications for treatment and severity of illness may have biased our observed associations. Additionally, the timing of outcomes of interest to determine the sequence of events was not impossible; therefore, an outcome event could have occurred prior to exposure effect, invalidating any speculation regarding causality. As a result of these limitations, we were not able to examine important outcomes, such as mortality, length of stay, or infectious complications, in relation to acid suppressant exposure in this cohort.
In conclusion, we examined recent prophylactic gastric acid–suppressant medication use in a PICU population. We found that these medications are prescribed in most patients and are increasing over time, particularly the use of PPI medications. Significant variation exists in the use of these medications that is associated with acute and chronic diagnoses, treatment with mechanical ventilation, and treatment hospital. Provider preference is a likely source for some of the observed variation. Gastrointestinal hemorrhage is rare in the current era. Limitations inherent in the study design prevent examination of causation of outcomes with acid suppressant exposure. Future investigations seem warranted to reexamine the value and adverse effects of these medications in PICU patients.
