John C. Keifer

Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers.

Background:Dexmedetomidine is a highly selective &agr;2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients. The analgesic profile of dexmedetomidine has not been fully characterized in humans. Methods:This study was designed to compare the analgesic responses of six healthy male volunteers during stepwise target-controlled infusions of remifentanil and dexmedetomidine. A computer-controlled thermode was used to deliver painful heat stimuli to the volar side of the forearms of the subjects. Six sequential 5-s stimuli (ranging from 41° to 50°C) were delivered in random order. The recorded visual analog scale was used to fit an Emax model. Results:Compared to baseline, remifentanil infusions resulted in a right shift of the sigmoid curve (increased T50, the temperature producing a visual analog scale score of 50% of the maximal effect, from 46.1°C at baseline to 48.4° and 49.1°C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients &ggr; during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T50 to 47.2°C) and a decrease in the steepness of the curve (decreased &ggr; from 3.24 during baseline and remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no difference in the pain responses between baseline and after recovery from remifentanil infusions (identical T50 and &ggr;). Conclusion:As expected, dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The difference in the quality of the analgesia with remifentanil may be a reflection of a different mechanism of action or a consequence of the sedative effect of dexmedetomidine.

A retrospective analysis of a remifentanil/propofol general anesthetic for craniotomy before awake functional brain mapping.

We performed this study to summarize drug dosing, physiologic responses, and anesthetic complications from an IV general anesthetic technique for patients undergoing craniotomy for awake functional brain mapping. Review of 98 procedures revealed “most rapid” IV infusion rates for remifentanil 0.05, 0.05–0.09 &mgr;g · kg−1 · min−1 and propofol 115, 100–150 &mgr;g · kg−1 · min−1. The infusions lasted for 78, 58-98 min. Intraoperative emergence from general anesthesia was 9 (6–13) min after discontinuing IV infusions to allow for brain mapping and was independent of infusion duration and duration of craniotomy before mapping. Spontaneous ventilation was generally satisfactory during drug infusion, as evidenced by Sao2 = 95% (92%–98%) and Paco2 = 50 (47–55) mm Hg. However, we recorded at least one 30-s epoch of apnea in 69 of 96 patients. Maximum systolic arterial blood pressure was 150 (139–175) mm Hg and minimal systolic arterial blood pressure was 100 (70–150) mm Hg during drug infusion. Three patients experienced intraoperative seizures. Two patients did not tolerate the awake state and required reinduction of general anesthesia. No patients required endotracheal intubation or discontinuation of surgery. This general anesthetic technique is effective for craniotomy with awake functional brain mapping and offers an alternative to continuous wakefulness or other IV sedation techniques.

Melatonin secretion after surgery

Sleep disturbance is common postoperatively. We examined whether melatonin concentrations were related to this disturbance in seven postoperative patients. Nocturnal concentrations of melatonin were significantly (p=0.005) lower on the first than on the second or third nights after surgery. This finding raises the possibility that melatonin suppression and associated sleep disturbance might be prevented by melatonin replacement.

The desaturation response time of finger pulse oximeters during mild hypothermia

Pulse oximeters may delay displaying the correct oxygen saturation during the onset of hypoxia. We investigated the desaturation response times of pulse oximeter sensors (forehead, ear and finger) during vasoconstriction due to mild hypothermia and vasodilation caused by glyceryl trinitrate. Ten healthy male volunteers were given three hypoxic challenges of 3 min duration under differing experimental conditions. Mild hypothermia increased the mean response time of finger oximeters from 130 to 215 s. Glyceryl trinitrate partly offset this effect by reducing the response time from 215 to 187 s. In contrast, the response times of the forehead and ear oximeters were unaffected by mild hypothermia, but the difference between head and finger oximeters was highly significant (p < 0.0001). The results suggest that the head oximeters provide a better monitoring site for pulse oximeters during mild hypothermia.

A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy.

BACKGROUND:Postoperative nausea and vomiting (PONV) occur commonly after craniotomy. In patients receiving prophylaxis with ondansetron and dexamethasone, vomiting occurred in 45% of patients at 48 hours. In addition to causing patient discomfort, the physical act of vomiting may increase intracranial pressure or cerebral intravascular pressure, jeopardizing hemostasis and cerebral perfusion. Aprepitant is a neurokin-1 receptor antagonist with a long duration of action and no sedative side effect. In a large multicenter study in patients undergoing abdominal surgery, aprepitant was significantly more effective than was ondansetron in preventing vomiting at 24 and 48 hours postoperatively. We hypothesized that the combination of aprepitant with dexamethasone will decrease the incidence of postoperative vomiting when compared with the combination of ondansetron and dexamethasone in patients undergoing craniotomy under general anesthesia. METHODS:Patients scheduled to undergo craniotomy under general anesthesia were enrolled in this prospective, double-blind, randomized study. Patients were randomized to receive oral aprepitant 40 mg (or matching placebo) 1 to 3 hours before induction of anesthesia or ondansetron 4 mg IV (or placebo) within 30 minutes of the end of surgery. All patients received dexamethasone 10 mg after induction of anesthesia. The anesthetic technique was standardized. Data were collected at regular intervals by blinded personnel for 48 hours after surgery. Statistical analysis was performed using Wilcoxons ranked sum test and &khgr;2 test. P < 0.05 was considered statistically significant. RESULTS:One hundred four patients completed the study. The cumulative incidence of vomiting at 48 hours was 16% in the aprepitant group and 38% in the ondansetron group (P = 0.0149). The incidence of vomiting was also decreased in the aprepitant group at 2 hours (6% vs. 21%, P = 0.0419) and 24 hours (14% vs. 36%, P = 0.0124). From 0 to 48 hours, there was no difference between the aprepitant and ondansetron groups in the incidence of nausea (69% vs. 60%), nausea scores, need for rescue antiemetics (65% vs. 60%), complete response (no PONV and no rescue, 22% vs. 36%), or patient satisfaction with the management of PONV. CONCLUSION:The combination of aprepitant and dexamethasone was more effective than was the combination of ondansetron and dexamethasone for prophylaxis against postoperative vomiting in adult patients undergoing craniotomy under general anesthesia. However, there was no difference between the groups in the incidence or severity of nausea, need for rescue antiemetics, or in complete response between the groups.

Transfusion-related Acute Lung Injury (TRALI) Complicating Colectomy for Ulcerative Colitis

TRANSFUSION-RELATED acute lung injury (TRALI) is a life-threatening complication that presents as adult respiratory distress syndrome after recent blood transfusion. The diagnosis may not be immediately obvious, especially if another systemic illness complicates the clinical picture. The immune basis of this transfusion reaction usually is caused by an incompatibility of recipient white cells and donor human leukocyte antigen (HLA) antibodies. Therefore, routine transfusion reaction evaluations, which explore erythrocyte incompatibilities, will fail to confirm the diagnosis. We report a case of TRALI, complicating colectomy for active ulcerative colitis. Postreaction immunologic evaluation clarified the pathogenesis of this event. Our findings point to the role of donor and recipient mediators. When transfusing blood during active inflammatory disease, minimizing potential white blood cell and serum interactions may be considered.

Neurophysiological intraoperative monitoring of the glossopharyngeal nerve: technical case report.

OBJECTIVE Neurophysiological intraoperative monitoring of the glossopharyngeal nerve has been performed only with needle electrodes inserted into the pharyngeal muscles or soft palate. We describe a noninvasive method of monitoring this cranial nerve. METHODS A 30-year-old man who presented with headache, as well as speech and swallowing difficulty, underwent surgical resection of a right vagus nerve schwannoma. Neurophysiological intraoperative monitoring of multiple lower cranial nerves, including the glossopharyngeal and vagus nerves, was performed. RESULTS The glossopharyngeal nerve was monitored with an adhesive surface electrode mounted on the cuff of a laryngeal mask airway, and the vagus nerve was monitored with a similar electrode mounted on the endotracheal tube. Successful monitoring allowed separation of the glossopharyngeal nerve from the tumor, and there was no postoperative swallowing deficit. CONCLUSION Monitoring of the glossopharyngeal nerve with surface electrodes is possible and reliable, but it must be combined with vagus nerve monitoring.

Changes in hematocrit based on incremental blood sampling: mathematical models perform poorly.

PurposeExcessive blood sampling, with its inherent risks, is of growing concern among clinicians. We performed this study to measure the changes in hematocrit (Hct) during a laboratory investigation where multiple blood samples are collected. The performance of a simple mathematical model, used in clinical practice to predict Hct changes, is evaluated.MethodsEight healthy male volunteers participated in this study. The equation Hctf = Hcti*(EBV-BL)/EBV is used to predict changes in Hct. Where Hctf and Hcti are, respectively, the final and initial Hct, EBV is the estimated blood volume and BL is the blood loss.ResultsThirty-five pharmacokinetic samples per subject were collected totalling 314 mL of BL.The Hct decreased from 44.2% ± 2.2% to 39.9% ± 2.5% (P = 0.001). On average, model predictions tended to have a discrete tendency to underestimate the Hct changes (-0.5% points of bias). While the predictions of the Hct were very accurate in 50% of the subjects, the discrepancy of the Hct predictions was clinically significant in the other 50% of the subjects.ConclusionConsistent with the model prediction, this study demonstrated a significant reduction in the Hct values in healthy subjects undergoing incremental phlebotomy. On average, the model successfully predicted the decrease in Hct. However, the inter- and intra-individual variabilities in the Hct changes are clinically significant. In clinical settings, which are not well controlled environments, the variability is likely to be greater and the clinical use of the model cannot replace the need to monitor the Hct.ObjectifLes échantillons sanguins excessifs, et leurs risques inhérents, préoccupent de plus en plus les cliniciens. Nous avons mesuré les modifications de l’hématocrite (Hct) au cours d’une investigation en laboratoire où de multiples échantillons sanguins sont prélevés. La performance d’un modèle mathématique simple, qui prédit les changements de l’Hct en clinique, est évaluée.MéthodeHuit hommes volontaires en santé ont participé à l’étude. L’équation Hctf = Hct*(VSE-PS)/VSE sert a prédire les changements de l’Hct où Hct et Hct sont respectivement l’Hct final et initial, VSE est le volume sanguin estimé et PS est la perte sanguine.RésultatsTrente-cinq échantillons pharmacocinétiques par sujet ont été prélevés pour un total de 314 mL de PS. L’Hct a diminué de 44,2 % ± 2,2 % à 39,9 % ± 2,5 % (P = 0,001). Les prédictions du modèle présentaient en moyenne une tendance discrète à sous-estimer les modifications de l’Hct (-0,5 % de biais). Les prédictions de l’Hct ont été très exactes chez 50 % des sujets, mais la divergence dans les prédictions était cliniquement significative chez les autres 50 %.ConclusionL’étude a démontré, conformément au modèle de prédiction, une réduction significative des valeurs de l’Hct chez des sujets sains qui subissent une phlébotomie incrémentielle. En moyenne, le modèle a pu prédire la baisse de l’Hct. Cependant, les variations interindividuelles et intra-individuelles de modification de l’Hct sont cliniquement significatives. En clinique, ce qui n’est pas un environnement bien conträlé, la variabilité risque d’être plus grande et l’usage clinique du modèle ne peut remplacer la nécessité du moniteur d’Hct.