Thrombocytopenia in intensive care patients: a comprehensive analysis of risk factors in 314 patients.

OBJECTIVE: To define the incidence and severity of thrombocytopenia in a mixed medical-surgical population of critically ill patients and to examine factors that may be related to the development of thrombocytopenia. DESIGN: Retrospective chart review of 314 critically ill patients requiring at least 3 days of critical care. SETTING: A 17-bed combined medical-surgical intensive care unit (ICU) in a 560-bed tertiary care community hospital. PATIENTS: Medical and surgical patients admitted to the ICU. INTERVENTIONS: All medical records over the duration of the ICU stay were reviewed. All scheduled medications, including dosage and start/stop dates, were recorded. All platelet counts, placement of pulmonary artery catheters, liver function test results, and admission serum creatinine concentrations were collected. MEASUREMENT AND MAIN RESULTS: Thrombocytopenia (platelet count less than 200 x 10(9)/L) was observed frequently, but rarely reached a severe stage (7 patients). No single diagnostic category was significantly associated with thrombocytopenia alone, although the combination of sepsis syndrome/septic shock and respiratory failure was strongly correlated (p < 0.0001) with thrombocytopenia. Liver function abnormalities were correlated strongly with thrombocytopenia, and the majority of patients (5 of 7) with severe thrombocytopenia (less than 20 x 10(9)/L) were found to have concurrent severe alterations in liver function test results. Pulmonary artery catheter placement and heparin exposure were associated strongly with thrombocytopenia (p < 0.0001). Drug therapies that were correlated with thrombocytopenia included heparin and vancomycin (p < 0.05). Hemodynamic instability was correlated strongly with the presence and severity of thrombocytopenia. In a stepwise linear regression model, the admission platelet count accounted for the largest proportion of the variance (43%), followed by hemodynamic instability (8%) and the requirement for inotropic agents (2%). CONCLUSIONS: Thrombocytopenia in the critically ill occurs frequently, rarely reaches severely depressed concentrations, and primarily represents a manifestation of disease processes initiated prior to admission. Hemodynamic instability and/or heparin exposure appear to be the strongest identifiable correlates with thrombocytopenia. Although these may cause infrequent isolated cases, other specific drug causes of thrombocytopenia are not responsible for the majority of cases of thrombocytopenia in the critically ill.

Randomized comparison of gastric pH control with intermittent and continuous intravenous infusion of famotidine in ICU patients.

OBJECTIVE: To compare gastric pH control using intravenous famotidine as a primed, continuous infusion versus intermittent infusion. METHODS: In a prospective, double-blind study, 40 ICU patients at risk for stress ulceration were randomly assigned to receive either famotidine 20 mg intravenous bolus followed by 1.67 mg/h infusion or famotidine 20 mg intravenously every 12 h. Intraluminal gastric pH was recorded at baseline and every 4 h using a glass electrode. Clinical outcome indicators were also monitored. Subjects were studied for a minimum of 24 h and a maximum of 6 days. Continuous variables were analyzed by ANOVA and nominal variables by Fisher's exact test (alpha = 0.05). RESULTS: Nineteen patients were randomized to the continuous infusion group, and 21 were randomized to the intermittent group. Using gastric pH greater than 4.0 as an endpoint, the continuous group exhibited better pH control, both in terms of percentage of total measurements (83% versus 63%, p < 0.001) and time spent above pH 4.0 (91% versus 76%, p < 0.01). Similar results were found at pH greater than 5.0 (78% versus 56% for all measurements for the continuous and bolus groups, respectively (p < 0.001), and 88% versus 72% for the time spent above pH 5.0 (p < 0.01). Clinical outcomes, including evidence for gastrointestinal bleeding and hospital mortality, did not differ significantly between groups. CONCLUSION: Famotidine infusion at 1.67 mg/h, when preceded by a bolus dose of 20 mg, provides a greater and more sustained increase in gastric pH than intermittent administration of famotidine 20 mg every 12 h.

Complete heart block and torsade de pointes associated with thioridazine poisoning.

A 72-year-old woman attempted suicide with thioridazine 3000 mg and 60 tablets of acetaminophen 325 mg plus codeine 30 mg. She was semicomatose and had persistent third-degree atrioventricular block, progressive hypotension, and an episode of torsade de pointes. Heart block, arrhythmias, and hypotension resolved within 48 hours, and the patient recovered without adverse sequelae.

Hepatotoxicity associated with angiotensin-converting enzyme inhibitors.

OBJECTIVE: To review published reports of hepatotoxicity associated with angiotensin-converting enzyme (ACE) inhibitors and to explore possible mechanisms of injury. DATA SOURCES: Published reports of hepatotoxicity associated with use of ACE inhibitors and investigations that suggest potential mechanisms of injury. DATA SYNTHESIS: Nineteen cases of ACE-inhibitor-associated hepatotoxicity are presented. Early theories regarding mechanisms are reviewed. Laboratory investigations of hepatic effects of eicosanoids on hepatic function are reviewed and a novel mechanism by which ACE inhibitors may cause hepatic injury is postulated. CONCLUSIONS: Hepatotoxicity, usually cholestatic in nature, has been reported with captopril, enalapril, and lisinopril use. Apparent cross-reactivity has been reported twice. Potential mechanisms of injury include idiopathic hypersensitivity and modulation of eicosanoid metabolism by inhibition of kininase II and subsequent increased hepatic bradykinin activity. Mediation via altered eicosanoid metabolism provides a plausible explanation for cross-reactivity among ACE inhibitors. Hepatotoxicity resolves if ACE inhibitors are stopped but may progress to liver failure if treatment is continued.

Sinus arrest associated with continuous-infusion cimetidine.

The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.

Suspected cross-reactivity of enalapril- and captopril-induced hepatotoxicity.

OBJECTIVE: To present evidence that enalapril and captopril may produce hepatotoxicity by a common mechanism. DATA SOURCES: A case report and review of pertinent literature. DATA SYNTHESIS: A patient developed hepatotoxicity once while taking enalapril and again while taking captopril. Hepatotoxicity resolved with cessation of therapy. Hepatotoxicity has been reported with use of captopril, enalapril, and lisinopril. Apparent cross-reactivity has been reported on just one other occasion. CONCLUSIONS: Because hepatotoxicity is uncommon with angiotensin-converting enzyme (ACE) inhibitors, our observations suggest the possibility that these agents produce hepatotoxicity by a common mechanism. In patients who develop hepatotoxicity while taking one ACE inhibitor, other agents in this class probably should be avoided.

Hemolytic-uremic syndrome associated with ingestion of quinine.

Hemolytic-uremic syndrome following quinine ingestion is a newly described phenomenon, with just two previous descriptions of 4 cases in the literature. We describe a 5th case. The reaction may be mediated by the presence of antibodies reactive against platelets in the presence of quinine. Treatment has included use of plasma exchange, prednisone, aspirin, and dipyridamole. The patients have all regained some degree of renal function. However, it is unclear whether pharmacological treatment or spontaneous resolution is responsible for the improvement. Quinine-associated hemolytic-uremic syndrome probably occurs more often than is recognized. It is important to recognize this reaction when it occurs and to avoid further quinine exposure, since the reaction seems to be recurrent.

Anaphylactoid reaction to intravenous acetylcysteine associated with electrocardiographic abnormalities.

OBJECTIVE: To review the potential for anaphylactoid reactions to intravenously administered acetylcysteine when used in the treatment of acetaminophen overdose. This case is unique in that electrocardiographic changes, including ST segment depression and T-wave inversion were associated with the episode and complicated the diagnosis. DATA SOURCES: Reference articles and letters are identified in the text. DATA SYNTHESIS: Intravenous administration of acetylcysteine has been used in the treatment of acetaminophen overdose. This route may be considered in some clinical situations where oral therapy is complicated. Anaphylactoid reactions, including cutaneous eruptions, flushing, chest pain, tachycardia, and fever have been reported in up to three percent of patients receiving intravenous acetylcysteine. The nature of these reactions and evidence concerning their etiology suggest a histamine-release phenomenon. Response to intervention with antihistamines and the safety of further acetylcysteine administration are discussed. CONCLUSIONS: This case illustrates a variant anaphylactoid reaction to intravenously administered acetylcysteine and emphasizes the need for practitioners to consider the potential for these reactions prior to initiation of therapy and indicates appropriate treatment of these reactions.

Study of antipsychotic drug use in long-term care facilities.

We chose to conduct this study because neuroleptic use has not been well defined in nursing homes. To our knowledge, it represents the only attempt at implementing the AIMS procedure in a group of nursing homes. We have provided evidence for what appears to be reasonably typical use of antipsychotic medication in skilled and intermediate care facilities. Senility and dementia were the most common diagnoses noted for neuroleptic recipients. Inservice education had little, if any, impact on antipsychotic drug use. Efforts to reduce the incidence of inappropriate use of neuroleptics should be aimed at physicians. We do feel that nursing and administrative staff are now more aware than previously of the dangers of indiscriminate use of these drugs. We feel that, because of our efforts, nursing staffs are better able to detect the presence of TD in their geriatric residents. If our sample of patients is representative of the entire population of institutionalized elderly, the overall rate of neuroleptic-induced TD may be lower than once thought. Similarly, the use of regularly scheduled neuroleptics in this population may be lower.