James P. Lynch

Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control.

Objective To determine the effect of intravenous glutamine supplementation vs. an isonitrogenous control on infectious morbidity in severely burned patients. Previous clinical studies in seriously ill patients suggest a beneficial effect of glutamine on infectious morbidity, but no trials have examined possible clinical benefits in severely burned patients. Design Prospective, double-blind, randomized trial. Setting Burn intensive care unit of a university hospital. Patients Twenty-six severe burn patients with total burn surface area of 25% to 90% and presence of full-thickness burns. Patients were evaluated for occurrence of bacteremia and antibiotic use during the first 30 days of their burn unit admission. Nutritional status and overall inflammation were also measured. Intervention Either intravenous glutamine or an isonitrogenous control amino acid solution was administered as a continuous infusion during burn intensive care unit stay. Measurements and Main Results The incidence of Gram-negative bacteremia was significantly reduced in the glutamine-supplemented group (8%) vs. control (43%;p < .04). No difference was seen in the incidence of Gram-positive bacteremia or fungemia. Average number of positive blood cultures, antibiotic usage, and mortality rates also were reduced but did not reach statistical significance. Significant improvements in serum transferrin and prealbumin were observed in glutamine-supplemented patients at 14 days after burn injury (p < .01 and .04, respectively). C-reactive protein was also significantly reduced at 14 days after burn injury in the glutamine group (p < .01). Conclusions Significantly fewer bacteremic episodes with Gram-negative organisms occurred in the glutamine-supplemented patients. Glutamine supplementation improved measures of nutrition and decreased measures of overall inflammation. In addition, a trend toward lower mortality rate, decreased overall bacteremia incidence, and antibiotic usage in the glutamine group was observed. Glutamine’s beneficial effects may be a result of improved gut integrity or immune function, but the precise mechanism of glutamine’s protection is unknown.

Tryptase Levels Are Not Increased during Vancomycin-induced Anaphylactoid Reactions

Background Anaphylaxis, mediated by immunoglobulin E, may be clinically indistinguishable but is mechanistically different than chemically mediated anaphylactoid reactions induced by drugs such as morphine, curare, and vancomycin. A test to distinguish anaphylactic from anaphylactoid reactions would clarify therapeutic and medicolegal issues. Tryptase levels identify anaphylactic reactions but have not been evaluated in vivo during anaphylactoid reactions. A prospective, randomized, double-blinded, placebo-controlled trial of antihistamine chemoprophylaxis for rapid vancomycin infusion was performed, and plasma tryptase was measured using a new immunoassay. Histamine release was established by measurement of plasma histamine and the ability of prophylactic H1 and H2 antagonists to prevent common histamine-associated side effects. Tryptase levels were compared with histamine levels and clinical symptoms. Methods Before elective arthroplasty, 40 patients received vancomycin infusion (1 g over 10 min) and pretreatment with either antihistamines (1 mg/kg diphenhydramine and 4 mg/kg cimetidine) or placebo. Changes in tryptase (at peak histamine and 10 min after vancomycin infusion), histamine levels, and histamine-mediated symptoms were assessed using Fishers exact test, the Students t test, or the paired t test, as appropriate. Logistic regression models were used to quantify the association of clinical symptoms with antihistamine treatment and serum levels. Results Plasma tryptase levels were unchanged (99% CI, -0.5 to 1.6) independent of increased histamine levels, antihistamine pretreatment, clinical symptoms, or all of these. Histamine levels >1 ng/ml were significantly associated with hypotension, moderate-to-severe rash, and stopped infusion. Antihistamine pretreatment significantly decreased the incidence and severity of the reactions. Conclusion Plasma tryptase levels were not significantly elevated in confirmed anaphylactoid reactions, so they can be used to distinguish chemical from immunologic reactions.

Prolonged sedation with propofol in the rat does not result in sleep deprivation.

The use of propofol provides sedation without prolonging emergence in patients in the Intensive Care Unit. When prolonged, however, continuous sedation may overlap with naturally occurring sleep periods and potentially increase the risk of sleep deprivation. We modified an established rat model of sleep to determine whether prolonged, continuous sedation results in sleep deprivation. Rats were continuously sedated for a 12-h period overlapping completely with their normal sleep phase. Electroencephalogram (EEG) and movement data were collected before and after the sedation period. Rats were evaluated for EEG and movement evidence of sleep deprivation after sedation. When compared with baseline, the time spent in rapid eye movement (REM) and non-REM sleep was decreased during the first 4 h after sedation. The duration of non-REM sleep bouts was not altered. Power in the &dgr; band (0.5–4 Hz) during non-REM sleep was diminished during the first 2 h only. Movements were reduced during the first hour after emergence from sedation only. In summary, no EEG or behavioral evidence of sleep deprivation was observed on emergence from sedation. These results imply that sedation is associated with a restorative process reversing the na-tural accumulation of sleep need that occurs during wakefulness.

Antihistamine prophylaxis permits rapid vancomycin infusion

OBJECTIVE To determine whether pretreatment with intravenous antihistamines attenuates the symptoms of red-man syndrome associated with rapid vancomycin administration. DESIGN Prospective, randomized, double-blinded, placebo-controlled study of patients undergoing elective arthroplasty. SETTING Preoperative unit in a tertiary care center. PATIENTS Forty preoperative patients (American Society of Anesthesiologists status I-III, receiving vancomycin prophylaxis for elective prosthetic joint replacement or revision. INTERVENTIONS Elective orthopedic patients were randomly allocated to receive intravenous antihistamines (diphenhydramine, 1 mg/kg, and cimetidine, 4 mg/kg) or placebo before rapid vancomycin infusion (1 g over 10 mins). Hemodynamic measurements, symptoms of histamine release, and plasma histamine levels were obtained in each patient during vancomycin administration. Rapid vancomycin infusion was discontinued in cases of decreases in mean blood pressure of > or =20% or intolerable itching. MEASUREMENTS AND MAIN RESULTS Clinical symptomatology of red-man syndrome and histamine levels were assessed using Fishers exact test or Students t-test. Comparison of baseline and peak histamine levels for both the treated (mean +/- SD, 0.2 +/- 0.2 vs. 4.7 +/- 2.4 ng/mL; p < .0001) and placebo patients (mean +/-SD, 0.2 +/- 0.1 vs. 3.5 +/- 3.4 ng/mL; p = .0002) was statistically significant. Although there was a significant increase in plasma histamine levels during vancomycin infusion, it did not differ between the treatment groups. Only two (11%) of the treated patients developed hypotension, vs. 12 (63%) of the placebo patients (p = .002). Rash was partially attenuated. Twelve (63%) of the treated patients developed rash, compared with 19 (100%) of the placebo patients (p = .008). The rapid infusion was discontinued in two (11%) of the treated patients, compared with 11 (58%) of the placebo patients (p = .005). Four treated patients had no symptoms of histamine release. CONCLUSIONS Pretreatment with intravenous H1 and H2 antihistamines permitted rapid vancomycin administration in 89% of treated patients. Although protection was incomplete, rash did not predict a need to stop the rapid infusion of vancomycin in our patients.

Dose‐related effects of oral acetaminophen on cold‐induced pain: A double‐blind, randomized, placebo‐controlled trial

The cold‐pressor test is a widely used pain‐induction model in humans. This method has been shown to be a sensitive measure for detecting opioid analgesia. However, nonsteroidal anti‐inflammatory drugs have not produced consistent analgesic effects with use of this model. The analgesic effect of acetaminophen (INN, paracetamol) on cold pressor‐induced pain has not been reported by other investigators. In this study, a double‐blind, randomized, placebo‐controlled design was used to evaluate the dose‐related effects of oral acetaminophen on cold pressor‐induced pain in 18 normal healthy human subjects. We observed dose‐related analgesic activity of oral acetaminophen using the cold pressor‐induced pain model in these subjects. There were statistically significant main effects of both dose and time (pain and bothersomeness ratings decreased with increasing drug dose and increased over time). In pairwise comparisons only the contrast between the highest dose of acetaminophen (1000 mg) and placebo reached statistical significance. Results from our study suggest that the cold‐pressor method may have clinical value in evaluating nonopioid analgesic agents.

The effect of premedication with OTFC, with or without ondansetron, on postoperative agitation, and nausea and vomiting in pediatric ambulatory patients.

Background : The purpose of this study was to evaluate, in the pediatric ambulatory surgical population, the efficacy of: (i) oral transmucosal fentanyl citrate (OTFC), when given preoperatively, to reduce postoperative excitement associated with sevoflurane, and (ii) intravenous ondansetron to reduce postoperative nausea and vomiting (PONV) associated with OTFC.

Histamine release during rapid vancomycin administration

Rapid administration of vancomycin induces red-man syndrome (RMS), characterised by rash (on the face, neck and torso), pruritus, and hypotension, attributed to histamine release [1–3]. Vancomycin stimulates histamine release by a chemically mediated anaphylactoid reaction [4]. The incidence of RMS can be reduced by infusion over 1 h which may be impractical in urgent clinical situations or ambulatory care. Other drug-induced, chemically mediated, anaphylactoid reactions can be attenuated by chemoprophylaxis with antihistamines [5–7]. The extent to which the manifestations of RMS are histamine-mediated has not been clearly established. We performed a prospective, randomised, double-blind, placebo-controlled study to investigate the correlation of RMS and histamine release and the ability of H1 and H2 antihistamines to attenuate RMS associated with rapid vancomycin administration.

A new biological assay for measuring cyanide in blood.

Clinical diagnosis of cyanide poisoning is complicated by the lack of an easy, convenient assay for cyanide concentration in blood.Therapy may be delayed with unconfirmed diagnosis because the conventional antidote to cyanide poisoning exposes patients to substantial risks. We developed a new spectrophotometric assay to measure cyanide by extraction into a sodium hydroxide trap, followed by the addition of exogenous methemoglobin as a colormetric indicator. Samples of blood from 15 healthy subjects and 5 patients who had received prolonged nitroprusside infusions were assayed. To optimize assay characteristics, methemoglobin concentrations, pH, temperature, incubation time, and buffer strengths were varied. Duplicate samples were assayed by using the polarographic method for assay validation. Over a range from 300 ng/mL to 7 micro g/mL, the correlation between methods was r = 0.983. Interassay and intraassay variability were 5% and 2%, respectively. Samples drawn from the five patients and tested by using both methods yielded a correlation of r = 0.978. This new assay for cyanide in blood may greatly facilitate the diagnosis and treatment of cyanide ingestion. The use of methemoglobin as the colorimetric indicator in the assay contributes to its low cost and ease of use. Implications: Cyanide, an important factor in death from burn-related inhalation injury, is difficult and time-consuming to measure. We developed a new, rapid blood test for cyanide using methemoglobin as a colormetric indicator. A rapid, accessible test for cyanide may speed the diagnosis and treatment of cyanide poisoning. (Anesth Analg 1997;85:1045-51)

Value of baseline levels in assessing tryptase release

Plasma tryptase may be useful in distinguishing between immune and chemically mediated reactions that can be clinically indistinguishable [1, 2]. In a recent study, only 7 out of 143 patients with life-threatening anaphylactic events of documented immune origin were tryptase negative [3]. In a previous study of 40 orthopedic patients who received vancomycin via rapid administration, we confirmed an anaphylactoid reaction. Tryptase levels were not increased despite 40-fold elevations in plasma histamine [4]. Thus, a tryptase assay potentially distinguishes between chemically and immunologically mediated reactions. Although our study of rapid vancomycin administration focused on the overall significance of elevations in tryptase levels, several additional facts emerged which suggest that serial tryptase levels may be important in characterizing the etiology of the reaction. We now specifically sought to assess whether isolated elevated tryptase levels, obtained at the peak of a reaction, would have altered our interpretation. Materials and methods