Jill A. Rebuck

Prevention of stress ulceration: current trends in critical care.

Objective:To identify the level of current intensivist’s knowledge regarding risk assessment and intensive care unit (ICU) clinical practice pertaining to stress-related mucosal bleeding, including pharmacologic approaches for stress ulcer prevention. Design:A nationwide survey of critical care physicians. Study Population:Two thousand random physician members of the Society of Critical Care Medicine. Measurements and Main Results:The response rate was 519 (26%) of 2000, with data analysis from 501 (25.1%) usable surveys. Respondents were affiliated with internal medicine (44.3%), surgery (42.3%), and anesthesiology (12.6%). Gut ischemia was indicated as the perceived major cause of stress ulceration (59.7%). The estimated incidence of clinically important bleeding was 2% or less by 62% of respondents; however, 28.6% of physicians surveyed initiate stress ulcer prophylaxis in all ICU patients, regardless of bleeding risk. Respiratory failure was most frequently indicated as a reason for stress ulcer prophylaxis (68.6%), followed by shock/hypotension (49.4%), sepsis (39.4%), and head injury/major neurologic insult (35.2%). The first-line agents selected for stress ulcer prophylaxis include histamine-2 receptor antagonists (63.9%), followed by proton pump inhibitors (23.1%), and sucralfate (12.2%). Concern for nosocomial pneumonia was regarded as more prevalent with antisecretory therapies in those who chose sucralfate (61%) as initial therapy compared with overall respondents (26.9%) (p < .001). Conclusions:The majority of intensivists surveyed recognize stress-related mucosal bleeding as a relatively infrequent event; however, implementation of a stress ulcer prophylaxis risk stratification scheme for ICU patients is necessary. Histamine-2 receptor antagonists are consistently perceived as appropriate initial agents, although proton pump inhibitors have become first-line therapy in an increasing percentage of critical care patients, despite limited data regarding their use in this population.

Pharmacokinetics of intravenous and oral levofloxacin in critically ill adults in a medical intensive care unit.

Study Objective. To characterize the pharmacokinetic disposition of intravenous and oral levofloxacin in critically ill adults.

Characterization of an Outbreak Due to Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae in a Pediatric Intensive Care Unit Transplant Population

Limited information exists regarding Klebsiella pneumoniaes production of an extended-spectrum beta-lactamase (KP-ESBL) in pediatric patients, particularly solid-organ transplant recipients. This study characterized the microbiological, epidemiological, and clinical features of a KP-ESBL outbreak in children receiving a liver transplant, an intestinal transplant, or both. All children found to have microbiologically confirmed K. pneumoniae during a 21-month period were reviewed. ESBL production was defined by double-disk diffusion, and 6 distinct pulsed-field gel electrophoresis patterns were identified. Fifty-six percent of the transplant patients we studied developed KP-ESBL, representing 87% of all microbiologically confirmed cases at our institution. As compared with 16 control transplant patients who were negative for KP-ESBL, the 20 transplant patients who acquired KP-ESBL were younger (aged < or = 5 years; 80.0% vs. 43.8%, P = .038) and experienced placement of > or = 3 central venous catheters before recovery of the first K. pneumoniae isolate (73.7% vs. 18.8%, P = .002). This study suggests that children who receive liver or intestinal transplants are at high risk for KP-ESBL acquisition.

Effect of once-daily dosing vs. multiple daily dosing of tobramycin on enzyme markers of nephrotoxicity

Objective:To determine the incidence of nephrotoxicity of once-daily dosing (ODD) and multiple daily dosing (MDD) regimens of tobramycin in critically ill patients. Design:Randomized, prospective clinical trial. Setting:Adult intensive care units at two university hospitals. Patients:Fifty-eight critically ill patients with a suspected or documented aerobic Gram-negative infection. Interventions:Patients were randomized to receive tobramycin by ODD (7 mg/kg) or MDD. Baseline urine aliquots and 24-hr urine collections were collected on days 3, 7, and 11 during therapy and on days 3, 7, and 11 following discontinuation of therapy for measurement of alanine aminopeptidase (AAP), N-acetyl-&bgr;-d-glucosaminidase (NAG), and creatinine. Measurements and Main Results:Fifty-four patients were evaluable (ODD n = 25; MDD n = 29). The groups were similar with regard to demographic and clinical variables. The tobramycin dose was higher in the ODD group compared with the MDD group (425 ± 122.5 mg vs. 312.8 ± 116.6 mg, p < .001). Patients in the MDD group received a mean of 3.89 ± 1.14 mg·kg−1·day−1 at intervals of 11.92 ± 3.12 hrs. In the ODD group, patients had a higher measured creatinine clearance at the end of therapy compared with MDD group (70 ± 18.6 vs. 64.8 ± 17.5 mL/min, p = .047). Fewer patients in the ODD group developed nephrotoxicity than the MDD group (5 vs. 12, p = .142). Although there were increases in urinary enzymes in both treatment groups (AAP, 8.7 ± 2.9 vs. 5.2 ± 2.1 units/24 hrs, p < .01 MDD vs. ODD; NAG, 14.7 ± 4.9 vs. 6.8 ± 3.1, p < .01 MDD vs. ODD), the increases in the ODD group were significantly lower than in the MDD group. Conclusions:The ODD tobramycin regimen appeared to be less nephrotoxic than the MDD regimen despite significantly higher doses. Tobramycin administered by ODD may be the preferred dosing method in selected critically ill medical patients to reduce the incidence and extent of renal damage.

Arthralgias and Myalgias Related to Quinupristin-Dalfopristin Administration

This study evaluated the frequency of and potential risk factors for arthralgias and/or myalgias associated with quinupristin-dalfopristin administration. Of 32 patients who received quinupristin-dalfopristin treatment, at least 15 (47%) developed arthralgias and/or myalgias. Clinicians should be aware of these adverse events associated with quinupristin-dalfopristin, which may occur more frequently than has been previously reported.

Survival of propofol infusion syndrome in a head-injured patient

Objective:To describe the clinical progression of an adult patient with traumatic brain injury who survived propofol infusion syndrome. Design:Case report. Setting:Tertiary care surgical intensive care unit. Patient:A 21-yr-old male with traumatic brain injury was administered high doses of propofol for sedation and intracranial pressure control combined with vasopressor therapy to maintain cerebral perfusion pressure >60 mmHg. He developed a significant metabolic acidosis with a lactic acid level of 10.9 mmol/L. Interventions:Exploratory laparotomy, discontinuation of propofol infusion. Measurements and Main Results:An exploratory abdominal laparotomy was negative for traumatic injury. During the procedure, the propofol infusion was considered a possible cause and was discontinued. On review, it became apparent that a combination of high-dose propofol and catecholamines were responsible for the lactic acidosis. An echocardiogram revealed severe left ventricular dysfunction and cardiomyopathy, which resolved within 19 days. Conclusions:High-dose propofol should be avoided and alternative agents should be instituted for sedation and intracranial pressure management. The use of catecholamine infusions to maintain cerebral perfusion pressure in the setting of a high-dose propofol infusion may be pharmacologically unsound and may be a triggering factor for propofol infusion syndrome. Identification of the syndrome and discontinuation of propofol resulted in complete reversal of symptoms in the case described.

Frequency of Inappropriate Continuation of Acid Suppressive Therapy After Discharge in Patients Who Began Therapy in the Surgical Intensive Care Unit

Study Objective. To determine the frequency with which patients who begin to receive stress ulcer prophylaxis in the surgical intensive care unit (SICU) are discharged receiving inappropriate acid suppressive therapy (AST).

The Critical Care Pharmacist: An Essential Intensive Care Practitioner

Clinical pharmacy services in the critical care setting have expanded dramatically and include assisting physicians in pharmacotherapy decision making, providing pharmacokinetic consultations, monitoring patients for drug efficacy and safety, providing drug information, and offering medical education to physicians, nurses, and patients. Measurable clinical effects of these services include reduced drug errors and adverse drug events, decreased morbidity and mortality rates, and a positive pharmacoeconomic impact by decreasing overall health care costs.

H2 Antagonist-induced thrombocytopenia: is this a real phenomenon?

Abstract. Critically ill patients routinely receive H2 antagonists for stress ulcer prophylaxis while at risk for gastrointestinal bleeding. In these patients it is often difficult to assess accurately the cause of adverse effects such as thrombocytopenia. We evaluate the literature to better define thrombocytopenia related to H2 antagonist administration and discuss mechanism, potential as a risk factor and case reports describing the severity and duration of thrombocytopenia.

A randomized, pharmacokinetic and pharmacodynamic, cross-over study of duodenal or jejunal administration compared to nasogastric administration of omeprazole suspension in patients at risk for stress ulcers.

OBJECTIVES:The aim of this study was to characterize absorption and pH control of simplified omeprazole suspension (SOS), 2 mg/ml in 8.4% sodium bicarbonate, administered via the nasogastric versus jejunal or duodenal route.METHODS:Nine critically ill surgical patients, NPO and mechanically ventilated, were enrolled in this randomized cross-over study. Patients received a single 40 mg dose of SOS by the nasogastric and either the jejunal or duodenal route. Twenty-four-hour continuous intragastric pH monitoring was performed during the study period. Sequential blood samples were collected over 24 h to characterize SOS absorption and pharmacokinetic parameters.RESULTS:Nasogastric administration of SOS resulted in lower maximum mean ± SD serum concentrations compared to jejunal/duodenal dosing (0.970 ± 0.436 vs 1.833 ± 0.416 μg/ml, p = 0.006). SOS absorption was significantly slower when administered via nasogastric tube (108.3 ± 42.0 vs 12.1 ± 7.9 min, p < 0.001). However, all routes of administration resulted in similar SOS area under the serum concentration–time curves (AUC0-∞) (415.1 ± 291.8 vs 396.7 ± 388.1 μg · h/ml, p = 0.91). Mean intragastric pH values remained >4 at 1 h after SOS administration and remained >4 for the entire 24-h study (6.32 ± 1.04, 5.57 ± 1.15, nasogastric vs jejunal/duodenal, p = 0.015), regardless of administration route.CONCLUSIONS:In critically ill surgical patients, pharmacokinetic parameters and subsequent pH control after the administration of SOS are similar by the jejunal, nasogastric, or duodenal route. SOS suspension offers an alternative acid control measure when patients are unable to take oral medications, yet have an enteral tube in place.