Maxim Rachinsky

Ketamine Attenuates the Interleukin-6 Response After Cardiopulmonary Bypass

Cardiopulmonary bypass (CPB) has been proposed as a model for studying the inflammatory cascade associated with the systemic inflammatory response syndrome.Serum interleukin-6 (IL-6) concentration seems to be a good indicator of activation of the inflammatory cascade and predictor of subsequent organ dysfunction and death. Prolonged increases of circulating IL-6 are associated with morbidity and mortality after cardiac operations. In the present study, we compared the effects of adding ketamine 0.25 mg/kg to general anesthesia on serum IL-6 levels during and after elective coronary artery bypass grafting (CABG). Thirty-one patients undergoing elective CABG were randomized to one of two groups and prospectively studied in a double-blind manner. The patients received either ketamine 0.25 mg/kg or a similar volume of isotonic sodium chloride solution in addition to large-dose fentanyl anesthesia. Blood samples for analysis of serum IL-6 levels were drawn before the operation; after CPB; 4, 24, and 48 h after surgery; and daily for 6 days beginning the third day postoperatively. Ketamine suppressed the serum IL-6 response immediately after CPB and 4, 24, and 48 h postoperatively (P < 0.05). During the first 7 days after surgery, the serum IL-6 levels in the ketamine group were significantly lower than those in the control group (P < 0.05). On Day 8 after surgery, IL-6 levels were no different from baseline values in both groups. A single dose of ketamine 0.25 mg/kg administered before CPB suppresses the increase of serum IL-6 during and after CABG. Implications: In this randomized, double-blind, prospective study of patients during and after coronary artery bypass surgery, we examined whether small-dose ketamine added to general anesthesia before cardiopulmonary bypass suppresses the increase of the serum interleukin-6 (IL-6) concentration. Serum IL-6 levels correlate with the patients clinical course during and after coronary artery bypass. Ketamine suppresses the increase of serum IL-6 during and after coronary artery bypass surgery. (Anesth Analg 1998;87:266-71)

Ketamine attenuates neutrophil activation after cardiopulmonary bypass.

UNLABELLED Surgery is associated with activation of neutrophils and their influx into affected tissue. The pathogenic role of superoxide production generated by activated neutrophils has been documented repeatedly. Ketamine suppresses neutrophil oxygen radical production in vitro. In the present study, we compared the effect of adding small-dose ketamine to opioids during the induction of general anesthesia on superoxide production by neutrophils after coronary artery bypass grafting (CABG). Thirty-five patients undergoing elective CABG were randomized to one of two groups and prospectively studied in a double-blinded manner. The patients received either ketamine 0.25 mg/kg or a similar volume of saline in addition to large-dose fentanyl anesthesia. Blood samples were drawn before the operation, immediately after cardiopulmonary bypass, 24 and 48 postoperative h, and on postoperative Days 3-6. Functional capacity of neutrophils was assessed by superoxide generation after stimulation with phorbol 12-myristate 13-acetate, opsonized zymosan, or formyl-methionyl-leucyl-phenylalanine. The addition of small-dose ketamine to general anesthesia attenuates increased production of the superoxide anion (O2-) by neutrophils without chemical stimulation and after stimulation with phorbol 12-myristate 13-acetate, formyl-methionyl-leucyl-phenylalanine, and opsonized zymosan for 4-6 days after CABG. In addition, ketamine attenuated the percentage of neutrophils on postoperative Days 2-6. In the Control group, superoxide production significantly increased compared with the baseline value. By contrast, in the Ketamine group, this difference was not significant. IMPLICATIONS In a randomized, double-blinded, prospective clinical study, we compared the effect of adding small-dose ketamine to opioids during general anesthesia on superoxide production and showed that ketamine suppressed the increase of superoxide anion production by neutrophils after coronary artery bypass grafting.

The effect of treatment with albumin, hetastarch, or hypertonic saline on neurological status and brain edema in a rat model of closed head trauma combined with uncontrolled hemorrhage and concurrent resuscitation in rats.

UNLABELLED In rats subjected to closed head trauma (CHT) plus uncontrolled hemorrhage, giving 0.3 mL of 0.9% saline per 0.1 mL of blood lost did not restore mean arterial blood pressure (MAP) or improve neurological severity score (NSS). In CHT without hemorrhage, giving 20% albumin or 10% hetastarch improved NSS. We hypothesized that these latter treatments would also improve NSS after CHT plus uncontrolled hemorrhage. Rats were randomly assigned to one of seven groups. Experimental conditions were CHT (yes or no), uncontrolled hemorrhage (yes or no), and fluid given to replace blood loss (none; 10% hetastarch, 20% albumin, or 3% saline [0.1 mL per 0.1 mL of blood lost]; or 0.9% saline [0.3 mL per 0.1 mL of blood lost]). NSS (0--25 scale, where 0 = no impairment) was determined at 1, 4, and 24 h, and brain water content was determined at 24 h after CHT. NSS (median +/- range) at 24 h was 11 +/- 6 when no fluid was given; 16 +/- 5 with 10% hetastarch; 14 +/- 5 with 20% albumin; 12 +/- 4 with 3% saline; and 13 +/- 4 with 0.9% saline given (not significant). In addition, brain water content and MAP did not differ among the groups receiving CHT with or without uncontrolled hemorrhage. In our model of CHT plus uncontrolled hemorrhage in rats, giving 10% hetastarch, 20% albumin, 3% saline, or 0.9% saline failed to improve NSS, brain water content, or MAP. IMPLICATIONS In previous studies of closed head trauma (CHT) without hemorrhage, giving 20% albumin or 10% hetastarch improved neurological severity scores (NSSs). We hypothesized that these treatments also might be beneficial in CHT plus uncontrolled hemorrhage. We found that giving 10% hetastarch, 20% albumin, 3% saline, or 0.9% saline failed to improve NSS, brain water content, or mean arterial blood pressure.

α-Adrenergic effects on low-frequency oscillations in blood pressure and R-R intervals during sympathetic activation.

The present study was designed to address the contribution of α‐adrenergic modulation to the genesis of low‐frequency (LF; 0.04–0.15 Hz) oscillations in R–R interval (RRi), blood pressure (BP) and muscle sympathetic nerve activity (MSNA) during different sympathetic stimuli. Blood pressure and RRi were measured continuously in 12 healthy subjects during 5 min periods each of lower body negative pressure (LBNP; −40 mmHg), static handgrip exercise (HG; 20% of maximal force) and postexercise forearm circulatory occlusion (PECO) with and without α‐adrenergic blockade by phentolamine. Muscle sympathetic nerve activity was recorded in five subjects during LBNP and in six subjects during HG and PECO. Low‐frequency powers and median frequencies of BP, RRi and MSNA were calculated from power spectra. Low‐frequency power during LBNP was lower with phentolamine versus without for both BP and RRi oscillations (1.6 ± 0.6 versus 1.2 ± 0.7 ln mmHg2, P = 0.049; and 6.9 ± 0.8 versus 5.4 ± 0.9 ln ms2, P = 0.001, respectively). In contrast, the LBNP with phentolamine increased the power of high‐frequency oscillations (0.15–0.4 Hz) in BP and MSNA (P < 0.01 for both), which was not observed during saline infusion. Phentolamine also blunted the increases in the LBNP‐induced increase in frequency of LF oscillations in BP and RRi. Phentolamine decreased the LF power of RRi during HG (P = 0.015) but induced no other changes in LF powers or frequencies during HG. Phentolamine resulted in decreased frequency of LF oscillations in RRi (P = 0.004) during PECO, and a similar tendency was observed in BP and MSNA. The power of LF oscillation in MSNA did not change during any intervention. We conclude that α‐adrenergic modulation contributes to LF oscillations in BP and RRi during baroreceptor unloading (LBNP) but not during static exercise. Also, α‐adrenergic modulation partly explains the shift to a higher frequency of LF oscillations during baroreceptor unloading and muscle metaboreflex activation.

Non-alpha-adrenergic effects on systemic vascular conductance during lower-body negative pressure, static exercise and muscle metaboreflex activation

This study tested the hypothesis that non‐α‐adrenergic mechanisms contribute to systemic vascular conductance (SVC) in a reflex‐specific manner during the sympathoexcitatory manoeuvres.

Adrenergic and myogenic regulation of viscoelasticity in the vascular bed of the human forearm

This study tested the hypothesis that the compliance (C) and viscoelasticity (K) of the forearm vascular bed are controlled by myogenic and/or α‐adrenergic receptor (αAR) activation. Heart rate (HR) and waveforms of brachial artery blood pressure (Finometer) and forearm blood flow (Doppler ultrasound) were measured in baseline conditions and during infusion of noradrenaline (NA; αAR agonist), with and without phentolamine (αAR antagonist; n= 10; 6 men and 4 women). These baseline and αAR‐agonist‐based measures were repeated when the arm was positioned above or below the heart to modify the myogenic stimulus. A lumped Windkessel model was used to quantify the values of forearm C and K in each set of conditions. Baseline forearm C was inversely, and K directly, related to the myogenic load (P < 0.001). Compared with saline infusion, C was increased, but K was unaffected, with phentolanine, but only in the ‘above’ position. Compliance was reduced (P < 0.001) and K increased (P= 0.06) with NA infusion (main effects of NA) across arm positions; phentolamine minimized these NA‐induced changes in C and K for both arm positions. Examination of conditions with and without NA infusion at similar forearm intravascular pressures indicated that the NA‐induced changes in C and K were due largely to the concurrent changes in blood pressure. Therefore, within the range of arm positions used, it was concluded that vascular stiffness and vessel wall viscoelastic properties are acutely affected by myogenic stimuli. Additionally, forearm vascular compliance is sensitive to baseline levels of αAR activation when transmural pressure is low.

The importance of kinin antagonist treatment timing in closed head trauma.

BACKGROUND Giving LF 16-0687 Ms (a bradykinin B2 receptor antagonist) 1 hour after closed head trauma (CHT) previously was reported to decrease brain edema at 24 hours and improve neurologic severity score (NSS) at 7 days. It is not certain whether a greater benefit could be achieved by treatment sooner after CHT. METHODS To examine the latter possibility we studied a surrogate condition for the earliest possible administration of LF 16-0687 Ms after CHT, e.g., we examined brain edema and NSS when LF 16-0687 Ms was given 15 min before CHT in rats. RESULTS LF 16-0687 Ms decreased brain water content (80.0 +/- 1.4%, mean +/- SD) at 24 hours and improved NSS (2 +/- 3, median +/- range) at 7 days after CHT in comparison to that with CHT + saline (82.9 +/- 1.3% and 8 +/- 4). CONCLUSION Similarity of the present results to those previously reported indicates that the benefit of giving LF 16-0687 Ms 1 hour after CHT appears to represent the maximal benefit afforded by this drug.

LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin E2 release in a rat model of closed head trauma combined with ethanol intoxication.

BACKGROUND LF 16-0687 Ms previously was reported to improve Neurological Severity Score (NSS) and decrease cerebral edema and prostaglandin E(2) (PGE(2)) release after closed head trauma (CHT) in rats. Here, we examined whether these beneficial effects of LF 16-0687 Ms are altered when CHT is accompanied by acute ethanol administration. METHODS Six groups of rats (n = 8 per group) were examined during combination of the following experimental conditions: CHT versus sham operation, LF 16-0687 Ms 3 mg/kg subcutaneously versus saline, and ethanol 2 g/kg versus saline. RESULTS After CHT, brain water content decreased and NSS improved with ethanol + LF 16-0687 Ms as compared with values after saline or ethanol. PGE(2) release decreased with ethanol (147 +/- 59 pg/mg tissue) but not with ethanol + LF 16-0687 Ms (286 +/- 194 pg/mg tissue). CONCLUSION Ethanol does not affect the improvement of NSS and the decrease of cerebral edema seen with LF 16-0687 Ms after CHT, but does reverse the ability of LF 16-0687 Ms to minimize the increase of PGE(2) release. In intoxicated patients, bradykinin antagonist therapy may improve post-CHT outcome without altering PGE(2) release.

Early Endotracheal Tube Insertion with the GlideScope: A Randomized Controlled Trial.

BACKGROUND:The GlideScope videolaryngoscope is an intubating device routinely used by anesthesiologists for tracheal intubation. It is occasionally difficult to advance the endotracheal tube (ETT) into the trachea, despite a good view of the glottis. One technique that may be used when difficulty is encountered is to remove the GlideScope from the pharynx and introduce the ETT into the pharynx first, leaving it in place posteriorly while the GlideScope is inserted. Frequently, when the GlideScope is subsequently inserted, the ETT tip will then be in good view, resting near the glottis, and will easily advance into the trachea. In this randomized, single-blinded trial, we assessed whether orotracheal intubation with the GlideScope is faster and/or easier with the ETT-first technique as a primary technique in elective patients. METHODS:One hundred sixty patients with normal-appearing airways who required elective orotracheal intubation were allocated randomly to intubation with insertion of the ETT or GlideScope into the oropharynx first. The primary outcome was time to intubation. The secondary outcomes were subjective ease of intubation (100-mm visual analog scale, 0 = easy; 100 = difficult), number of attempts/failures, incidence of oropharyngeal bleeding, and postoperative sore throat and/or vocal changes. RESULTS:Baseline demographics were similar between the 2 groups. Mean time to intubation was 48.2 ± 17.1 seconds with the ETT-first technique and 51.5 ± 21.8 seconds with the GlideScope-first technique (P = 0.30). The mean difference was 3.3 seconds in favor of the ETT-first technique (95% confidence interval, −2.9 to 9.6). The median ease of intubation using the visual analog scale was 13.3 mm (interquartile range, 5.3 to 21) with the ETT-first technique and 13.5 mm (interquartile range, 5.6 to 29.5) with the GlideScope-first technique (P = 0.30). The difference between the medians was −2.0 mm in favor of the ETT-first group (95% confidence interval, −1.5 to 6.0). There was no difference between groups for number of intubation attempts, incidence of oropharyngeal bleeding, laryngoscopic grade, sore throat, or vocal changes. CONCLUSIONS:In this study of GlideScope laryngoscopy, no statistically significant difference was observed in the time to intubate or the subjective ease of intubation whether the ETT or GlideScope was inserted into the oropharynx first.

Augmented Reality Guidance System for Peripheral Nerve Blocks

Peripheral nerve block treatments are ubiquitous in hospitals and pain clinics worldwide. State of the art techniques use ultrasound (US) guidance and/or electrical stimulation to verify needle tip location. However, problems such as needle-US beam alignment, poor echogenicity of block needles and US beam thickness can make it difficult for the anesthetist to know the exact needle tip location. Inaccurate therapy delivery raises obvious safety and efficacy issues. We have developed and evaluated a needle guidance system that makes use of a magnetic tracking system (MTS) to provide an augmented reality (AR) guidance platform to accurately localize the needle tip as well as its projected trajectory. Five anesthetists and five novices performed simulated nerve block deliveries in a polyvinyl alcohol phantom to compare needle guidance under US alone to US placed in our AR environment. Our phantom study demonstrated a decrease in targeting attempts, decrease in contacting of critical structures, and an increase in accuracy of 0.68 mm compared to 1.34mm RMS in US guidance alone. Currently, the MTS uses 18 and 21 gauge hypodermic needles with a 5 degree of freedom sensor located at the needle tip. These needles can only be sterilized using an ethylene oxide process. In the interest of providing clinicians with a simple and efficient guidance system, we also evaluated attaching the sensor at the needle hub as a simple clip-on device. To do this, we simultaneously performed a needle bending study to assess the reliability of a hub-based sensor.