A comparison of epinephrine and norepinephrine in critically ill patients

Objective  To determine whether there was a difference between epinephrine and norepinephrine in achieving a mean arterial pressure (MAP) goal in intensive care (ICU) patients. Design  Prospective, double-blind, randomised-controlled trial. Setting  Four Australian university-affiliated multidisciplinary ICUs. Patients and participants  Patients who required vasopressors for any cause at randomisation. Patients with septic shock and acute circulatory failure were analysed separately. Interventions  Blinded infusions of epinephrine or norepinephrine to achieve a MAP ≥70 mmHg for the duration of ICU admission. Measurements  Primary outcome was achievement of MAP goal >24 h without vasopressors. Secondary outcomes were 28 and 90-day mortality. Two hundred and eighty patients were randomised to receive either epinephrine or norepinephrine. Median time to achieve the MAP goal was 35.1 h (interquartile range (IQR) 13.8–70.4 h) with epinephrine compared to 40.0 h (IQR 14.5–120 h) with norepinephrine (relative risk (RR) 0.88; 95% confidence interval (CI) 0.69–1.12; P = 0.26). There was no difference in the time to achieve MAP goals in the subgroups of patients with severe sepsis (n = 158; RR 0.81; 95% CI 0.59–1.12; P = 0.18) or those with acute circulatory failure (n = 192; RR 0.89; 95% CI 0.62–1.27; P = 0.49) between epinephrine and norepinephrine. Epinephrine was associated with the development of significant but transient metabolic effects that prompted the withdrawal of 18/139 (12.9%) patients from the study by attending clinicians. There was no difference in 28 and 90-day mortality. Conclusions  Despite the development of potential drug-related effects with epinephrine, there was no difference in the achievement of a MAP goal between epinephrine and norepinephrine in a heterogenous population of ICU patients. This study was presented at the Annual Congress of the European Society of Intensive Care Medicine in Berlin on October 10 2007. The presentation received the International Sepsis Forum prize for best abstract and paper. This study has been published in abstract form: Myburgh J.A., Higgins A., Jovanovska A., Lipman J., Ramakrishnan N., Santamaria J and the CAT Study Investigators. (2007). A comparison of epinephrine and norepinephrine on reversal of shock. Intensive Care Medicine 33 (Supplement 2): S197. Trial registration: The study was registered with Current Controlled Studies: ISRCTN number 92846592.     

Acute respiratory distress in a bleomycin primed patient: a new use for nitric oxide

We describe the use of nitric oxide as an oxygen-sparing strategy in the context of prior bleomycin exposure. A 27-year-old male, previously treated with bleomycin for a testicular germ cell tumour presented with severe acute respiratory distress syndrome on the second postoperative day following an extensive retroperitoneal dissection. The mechanism of bleomycin toxicity and potential benefits of nitric oxide in this situation are considered.     

A community outbreak of Legionnaires' disease linked to hospital cooling towers: an epidemiological method to calculate dose of exposure.

BACKGROUND: From July to September 1994, 29 cases of community-acquired Legionnaires' disease (LD) were reported in Delaware. The authors conducted an investigation to a) identify the source of the outbreak and risk factors for developing Legionella pneumophila serogroup 1 (Lp-1) pneumonia and b) evaluate the risk associated with the components of cumulative exposure to the source (i.e. distance from the source, frequency of exposure, and duration of exposure). METHODS: A case-control study matched 21 patients to three controls per case by known risk factors for acquiring LD. Controls were selected from patients who attended the same clinic as the respective case-patients. Water samples taken at the hospital, from eight nearby cooling towers, and from four of the patient's homes were cultured for Legionella. Isolates were subtyped using monoclonal antibody (Mab) analysis and arbitrarily primed polymerase chain reaction (AP-PCR). RESULTS: Eleven (52%) of 21 case-patients worked at or visited the hospital compared with 17 (27%) of 63 controls (OR 5.0, 95% CI : 1.1-29). For those who lived, worked, or visited within 4 square miles of the hospital, the risk of illness decreased by 20% for each 0.10 mile from the hospital; it increased by 80% for each visit to the hospital; and it increased by 8% for each hour spent within 0.125 miles of the hospital. Lp-1 was isolated from three patients and both hospital cooling towers. Based on laboratory results no other samples contained Lp-1. The clinical and main-tower isolates all demonstrated Mab pattern 1,2,5,6. AP-PCR matched the main-tower samples with those from two case-patients. CONCLUSION: The results of our investigation suggested that the hospital cooling towers were the source of a community outbreak of LD. Increasing proximity to and frequency of exposure to the towers increased the risk of LD. New guidelines for cooling tower maintenance are needed. Knowing the location of cooling towers could facilitate maintenance inspections and outbreak investigations.     

Amoxicillin-clavulanic acid and trimethoprim- sulfamethoxazole in rodent feed and water: effects of compounding on antibiotic stability.

We assessed the concentrations of 2 antibiotic combinations, amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole when compounded in reverse osmosis [RO] (pH 6.0), tap (pH 6.7), and acidified water (pH 2.6) over 7 d, and pre- and post-pelleting, post-gamma irradiation and shipping, and monthly until 180 d post-milling in feed. Amoxicillin concentrations in RO and tap water varied between 1.18 and 1.29 mg/ml, and 1.09 and 1.22 mg/ml, respectively. The concentration of amoxicillin declined immediately and remained between 0.43 and 0.50 mg/ml in acidified water. Clavulanic acid exhibited a slow time-dependent decrease in concentration to 0.05 mg/ml at day 7 in RO water, immediately declined and varied from 0.02 to 0.05 mg/ml in tap water, and was undetectable in acidified water. Trimethoprim and sulfamethoxazole concentrations were near expected in RO, tap, and acidified water. In food, amoxicillin, trimethoprim, and sulfamethoxazole concentrations were each reduced to approximately 60% of expected after pelleting, but remained stable thereafter for 180 d. The initial clavulanic acid concentration in feed was less than 10% of expected and was undetectable after 1 mo. Plasma drug concentrations were determined in C57BL/6NCrl mice at 4 h after commencement of the dark and light cycles following administration of antibiotic food for at least 72 h. Plasma amoxicillin and sulfamethoxazole concentrations were 3- and 10-fold greater, respectively, during the dark period. Plasma levels of clavulanic acid and trimethoprim were consistent at both time points. These results indicate that the antibiotic concentration can be influenced by compounding in feed and water, and differs in plasma during the light and dark phases of the photoperiod.