Prevention of acute gastrointestinal complications after severe head injury: A controlled trial of cimetidine prophylaxis

doi:10.1016/0002-9610(80)90228-7

The American Journal of Surgery

Volume 139, Issue 1, January 1980, Pages 44-48

https://doi.org/10.1016/0002-9610(80)90228-7 Get rights and content

Abstract

Cimetidine prophylaxis significantly reduced the risk of gastrointestinal bleeding after severe head injury in this prospective, double-blind clinical trial. Cimetidine effectively reduced both the volume and the acidity of gastric secretions after brain injury without producing adverse side effects. The most common endoscopic finding was superficial, erosive, mucosal lesions in the proximal stomach. Cimetidine prophylaxis was not shown to reduce the incidence of these lesions in this study but did diminish their severity and the likelihood that they would complicate the management of these patients.

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Prophylactic acid suppressants in patients with primary neurologic injury: A systematic review and meta-analysis of randomized controlled trials
2022, Journal of Critical Care
Citation Excerpt :
Of the included trials, 5 (36%) were performed in the United States, 2 were performed in China (14%), 2 were performed in India (14%), and 1 each in Czech Republic, Taiwan, Switzerland, Iran, and Indonesia. A total of 5 trials examined H2RAs compared to placebo [14,27,28,30,36], 2 trials examined H2RAs compared to no intervention [32,37], 1 trial examined PPIs compared to no intervention [29], and 4 trials compared PPIs to H2RAs [26,34,35,38] (See Table 1). Of note, 1 trial examined PPIs and H2RAs as a 3-arm trial with a placebo group [35] and 2 trials compared medications in the same pharmacological class (PPIs) [31,33].
Neurocritical care patients are at risk of stress-induced gastrointestinal ulceration. We performed a systematic review and meta-analysis of stress ulcer prophylaxis (SUP) in critically ill adults admitted with a primary neurologic injury.
We included randomized controlled trials (RCTs) comparing SUP with histamine-2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) to placebo/no prophylaxis, as well as to each other. The primary outcome was in-ICU gastrointestinal bleeding (GIB). Predefined secondary outcomes were all-cause 30-day mortality, ICU length of stay (LOS), nosocomial pneumonia, and other complications.
We identified 14 relevant trials enrolling 1036 neurocritical care patients; 11 trials enrolling 930 patients were included in the meta-analysis. H2RAs resulted in a lower incidence of GIB as compared to placebo or no prophylaxis (Risk ratio [RR] 0.42, 95% CI 0.30–0.58; p < 0.001); PPIs with a lower risk of GIB compared to placebo/no prophylaxis (RR 0.37, 95% CI 0.23–0.59; p < 0.001). No significant difference was observed in GIB comparing PPIs with H2RAs (RR 0.53, 95% CI 0.26–1.06; p = 0.07; I² = 0%).
In neurocritical care patients, the overall high or unclear risk of bias of individual trials, the low event rates, and modest sample sizes preclude strong clinical inferences about the utility of SUP.
Effects of Yunanan Baiyao adjunct therapy on postoperative recovery and clinical prognosis of patients with traumatic brain injury: A randomized controlled trial
2021, Phytomedicine
Citation Excerpt :
YB showed significantly better anti-bleeding efficacy (92.30%) than pantoloc (71.20%) in severe TBI-induced stress gastrointestinal bleeding and ulcer (Xu and Ma, 2009; Wang and Dong, 2010) and is more effective in controlling gastrointestinal tract inflammation in colitis model of inflammatory bowel disease (IBD), by suppressing pro-inflammatory cytokine expression (including TNFa, IL-12p40, and IL-17) and T- and B-lymphocytes, and but promoting intestinal epithelial wound-healing/repairing (Li et al., 2011). Gastrointestinal bleeding and dysfunction are common complications of TBI (developed in up to 80% of severe TBI) (Halloran et al., 1980; Gudeman et al., 1983; Muller et al., 1988; Hang et al., 2003). Intracerebral hemorrhage destroys gut mucosa and intestinal barrier, increases plasma levels of malondialdehyde (MDA) and reactive oxygen species (ROS), endotoxin, inflammatory cytokines and oxidative stress, but decreases SOD activity in mice (Cheng et al., 2018).
Effective therapies are needed to prevent the secondary injury and poor prognosis associated with emergency craniotomy of traumatic brain injury (TBI).
The wound-healing medicine Yunnan Baiyao (YB) and Xingnaojing (XNJ) adjunct-therapy may improve the outcome of orthodox mono-therapy (OT).
Randomized controlled trial.
Eighty patients with moderate-to-severe TBI received emergency craniotomy (within 12 h after TBI) at the Chinese PLA General Hospital before being randomly assigned to 4 different treatments (n = 20) for 7 days: 1) OT; 2) OT+XNJ (i.v. 20 ml/daily); 3) OT+low dose-YB (oral, 1,000 mg/day); 4) OT+high dose-YB, 2,000 mg/day).
GCS score was improved more quickly and became significantly higher in XNJ, l-YB, h-YB groups than in OT group (p<0.01). Serum S100B peaked higher but declined more slowly in OT group than in other groups (p<0.01). On postoperative Day 7, S100B was 20% below baseline in YB and XNJ groups but remained 19% above baseline in OT group which also lost 38% of superoxide dismutase (SOD) activity on Day 3 and recovered 69% of SOD on Day 7 whereas the YB and XNJ groups lost 16%∼23% of SOD activity on Day 3 and recovered 92%∼99% of SOD on Day 7 (p<0.01). Clinical prognosis (Glasgow Outcome Scale and Karnofsky Performance Scale) were significantly better (25%∼30%) in the XNJ, l-YB and h-YB groups than in OT group 3 months post-surgery and were correlated with serum S100B and SOD.
YB and XNJ adjunct therapies improved postoperative recovery and clinical prognosis in patients with moderate-to-severe TBI partly through divergent regulation of S100B and SOD pathways. (The trial was registered at Chinese Clinical Trial Registry (ChiCTR) trial registration number: ChiCTR2000030280)
Acute Management of Traumatic Brain Injury
2017, Surgical Clinics of North America
Perioperative Management of Severe Traumatic Brain Injury in Adults
2012, Schmidek and Sweet Operative Neurosurgical Techniques: Indications, Methods, and Results: Sixth Edition
Gastric Mucosal Defense and Cytoprotection: Bench to Bedside
2008, Gastroenterology
Citation Excerpt :
Bleeding from these mucosal lesions tends to be slow; if massive bleeding occurs, it suggests that an ulcer (ie, extension below the mucosa) has developed. Overt bleeding (eg, bloody nasogastric aspirate, hematemesis, melena) is reported in ∼20% of critically ill patients; pooled results from placebo/no therapy control groups of 10 randomized controlled trials in metaanalyses of prophylactic therapy performed from 1980 to 1998120,121,123–132 reveal an incidence of 17%. However, the most relevant outcome to consider is clinically significant bleeding.
The gastric mucosa maintains structural integrity and function despite continuous exposure to noxious factors, including 0.1 mol/L HCl and pepsin, that are capable of digesting tissue. Under normal conditions, mucosal integrity is maintained by defense mechanisms, which include preepithelial factors (mucus-bicarbonate-phospholipid “barrier”), an epithelial “barrier” (surface epithelial cells connected by tight junctions and generating bicarbonate, mucus, phospholipids, trefoil peptides, prostaglandins (PGs), and heat shock proteins), continuous cell renewal accomplished by proliferation of progenitor cells (regulated by growth factors, PGE₂ and survivin), continuous blood flow through mucosal microvessels, an endothelial “barrier,” sensory innervation, and generation of PGs and nitric oxide. Mucosal injury may occur when noxious factors “overwhelm” an intact mucosal defense or when the mucosal defense is impaired. We review basic components of gastric mucosal defense and discuss conditions in which mucosal injury is directly related to impairment in mucosal defense, focusing on disorders with important clinical sequelae: nonsteroidal anti-inflammatory drug (NSAID)-associated injury, which is primarily related to inhibition of cyclooxygenase (COX)-mediated PG synthesis, and stress-related mucosal disease (SRMD), which occurs with local ischemia. The annual incidence of NSAID-associated upper gastrointestinal (GI) complications such as bleeding is approximately 1%–1.5%; and reductions in these complications have been demonstrated with misoprostol, proton pump inhibitors (PPIs) (only documented in high-risk patients), and COX-2 selective inhibitors. Clinically significant bleeding from SRMD is relatively uncommon with modern intensive care. Pharmacologic therapy with antisecretory drugs may be used in high-risk patients (eg, mechanical ventilation ≥48 hours), although the absolute risk reduction is small, and a decrease in mortality is not documented.
Stress ulcer prophylaxis in the new millennium: A systematic review and meta-analysis
2010, Critical Care Medicine
Recent observational studies suggest that bleeding from stress ulceration is extremely uncommon in intensive care unit patients. Furthermore, the risk of bleeding may not be altered by the use of acid suppressive therapy. Early enteral tube feeding (initiated within 48 hrs of intensive care unit admission) may account for this observation. Stress ulcer prophylaxis may, however, increase the risk of hospital-acquired pneumonia and Clostridia difficile infection.
A systematic review of the literature to determine the benefit and risks of stress ulcer prophylaxis and the moderating effect of enteral nutrition.
MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles.
Randomized, controlled studies that evaluated the association between stress ulcer prophylaxis and gastrointestinal bleeding. We included only those studies that compared a histamine-2 receptor blocker with a placebo.
Data were abstracted on study design, study size, study setting, patient population, the histamine-2 receptor blocker and dosage used, the incidence of clinically significant gastrointestinal bleeding, hospital-acquired pneumonia, mortality, and the use of enteral nutrition.
Seventeen studies (which enrolled 1836 patients) met the inclusion criteria. Patients received adequate enteral nutrition in three of the studies. Overall, stress ulcer prophylaxis with a histamine-2 receptor blocker reduced the risk of gastrointestinal bleeding (odds ratio 0.47; 95% confidence interval, 0.29-0.76; p < .002; I² = 44%); however, the treatment effect was noted only in the subgroup of patients who did not receive enteral nutrition. In those patients who were fed enterally, stress ulcer prophylaxis did not alter the risk of gastrointestinal bleeding (odds ratio 1.26; 95% confidence interval, 0.43-3.7). Overall histamine-2 receptor blockers did not increase the risk of hospital-acquired pneumonia (odds ratio 1.53; 95% confidence interval, 0.89-2.61; p = .12; I² = 41%); however, this complication was increased in the subgroup of patients who were fed enterally (odds ratio 2.81; 95% confidence interval, 1.20-6.56; p = .02; I² = 0%). Overall, stress ulcer prophylaxis had no effect on hospital mortality (odds ratio 1.03; 95% confidence interval, 0.78-1.37; p = .82). The hospital mortality was, however, higher in those studies (n = 2) in which patients were fed enterally and received a histamine-2 receptor blocker (odds ratio 1.89; 95% confidence interval, 1.04-3.44; p = .04, I² = 0%). Sensitivity analysis and meta-regression demonstrated no relationship between the treatment effect (risk of gastrointestinal bleeding) and the classification used to define gastrointestinal bleeding, the Jadad quality score nor the year the study was reported.
The results of this meta-analysis suggest that, in those patients receiving enteral nutrition, stress ulcer prophylaxis may not be required and, indeed, such therapy may increase the risk of pneumonia and death. However, because no clinical study has prospectively tested the influence of enteral nutrition on the risk of stress ulcer prophylaxis, our findings should be considered exploratory and interpreted with some caution.

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^☆: This work was supported by a grant from Smith, Kline and French Laboratories, Philadelphia, Pennsylvania, and Grant NS 12587 from the National Institutes of Health, Bethesda, Maryland.

^☆☆: Presented at the 20th Annual Meeting of the Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 22–23, 1979.

¹: From the Departments of Surgery and Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia.

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Scientific paperPrevention of acute gastrointestinal complications after severe head injury: A controlled trial of cimetidine prophylaxis☆,☆☆

Abstract

Am J Surg

Gastrointestinal bleeding following head injury: a clinical study of 433 cases

J Trauma

Gastric secretory response to head injury

Arch Surg

Hemorrhage due to diffuse erosive gastritis

Arch Surg

Gastric acidity in the comatose patient

J Neurosurg

Natural history and surgical dilemma of “stress” gastric bleeding

Arch Surg

The surgical management of stress ulcers

Ann Surg

Studies of gastric secretion in stressed patients

Ann Surg

Prospective study of gastric secretion in stressed patients with intracranial injury

J Trauma

Scientific paper
Prevention of acute gastrointestinal complications after severe head injury: A controlled trial of cimetidine prophylaxis☆,☆☆