Erythrocyte cell membranes undergo morphologic changes during storage, but it is unclear whether these changes are reversible. We assessed erythrocyte cell membrane deformability in patients before and after transfusion to determine the effects of storage duration and whether changes in deformability are reversible after transfusion.

Sixteen patients undergoing posterior spinal fusion surgery were studied. Erythrocyte deformability was compared between those who required moderate transfusion (≥5 units erythrocytes) and those who received minimal transfusion (0–4 units erythrocytes). Deformability was measured in samples drawn directly from the blood storage bags before transfusion and in samples drawn from patients before and after transfusion (over 3 postoperative days). In samples taken from the blood storage bags, we compared deformability of erythrocytes stored for a long duration (≥21 days), those stored for a shorter duration (<21 days), and cell-salvaged erythrocytes. Deformability was assessed quantitatively using the elongation index (EI) measured by ektacytometry, a method that determines the ability for the cell to elongate when exposed to shear stress.

Erythrocyte deformability was significantly decreased from the preoperative baseline in patients after moderate transfusion (EI decreased by 12% ± 4% to 20% ± 6%; P = 0.03) but not after minimal transfusion (EI decreased by 3% ± 1% to 4% ± 1%; P = 0.68). These changes did not reverse over 3 postoperative days. Deformability was significantly less in erythrocytes stored for ≥21 days (EI = 0.28 ± 0.02) than in those stored for <21 days (EI = 0.33 ± 0.02; P = 0.001) or those drawn from patients preoperatively (EI = 0.33 ± 0.02; P = 0.001). Cell-salvaged erythrocytes had intermediate deformability (EI = 0.30 ± 0.03) that was greater than that of erythrocytes stored ≥21 days (P = 0.047), but less than that of erythrocytes stored <21 days (P = 0.03).

The findings demonstrate that increased duration of erythrocyte storage is associated with decreased cell membrane deformability and that these changes are not readily reversible after transfusion.

Nerve-stimulated fade in muscle is generally accepted as a prejunctional phenomenon mediated by block of prejunctional acetylcholine receptors (AChRs) at the nerve terminal, whereas decrease of twitch tension is considered a postjunctional effect due to block of muscle AChRs. Using ligands with specific pre- or postjunctional effects only, we tested the hypothesis that fade is not necessarily a prejunctional phenomenon.

Neuromuscular function in rats was evaluated after IM (2.5 U) or IV (12.0 U) injection of botulinum toxin (Botx), or IV (250 μg/kg) α-bungarotoxin (α-BTX) alone. The acute neuromuscular effects of IV 2 mg/kg dihydro-β-erythroidine (DHβE), alone and in combination with α-BTX, were also tested. Botx decreases vesicular release of ACh, and α-BTX binds to postjunctional nicotinic AChRs only, whereas DHβE binds specifically to prejunctional α3β2 AChRs only. In view of the lack of acute effects of Botx even at 2 hours after IV injection, its neuromuscular effects were also evaluated at 24 hours after IM injection (0.6 U) and compared with IM injection of α-BTX (25 μg/kg) or saline also given 24 hours earlier. The sciatic nerve-tibialis muscle preparation, during train-of-four and tetanic stimulation, was used to test neuromuscular effects in vivo.

IV and IM Botx had no observable neuromuscular effects at 2 hours. IV α-BTX caused twitch depression within a few minutes, and significant fade (P = 0.002) at 75% of baseline twitch tension; these effects persisted until the end of the observation period of 2 hours. IV DHβE alone caused no significant change in single twitch (P = 0.899) or train-of-four ratio (P = 0.394), but significantly enhanced the fade of IV α-BTX (P = 0.001 at 75% of baseline twitch tension). IM Botx or α-BTX, at 24 hours after their injection, resulted in a significant decrease of single twitch and tetanic tensions (P < 0.0001), but Botx did not cause fade, whereas α-BTX caused significant (P < 0.0001) fade at 24 hours. The tibialis muscle weights and protein expression of α1 subunit of AChR (Western blots) did not differ between Botx, α-BTX and saline-injected groups at 24 hours but increased in denervated muscle (positive control).

Botx-induced decreased ACh release in and of itself does not cause fade but does cause decrease of absolute tensions. Decrease of available (functional) postjunctional AChRs by α-BTX did induce fade. The prejunctional fade effects of DHβE on α3β2 AChRs become manifest only when the margin of safety was decreased by concomitant administration of α-BTX. Thus, fade during repetitive stimulation is not always a prejunctional phenomenon and may also reflect the decreased margin of safety of neurotransmission, which can be due to a pure postjunctional AChRs block or to a combination of both pre- and postjunctional AChRs block. Block of prejunctional α3β2 AChRs alone is not necessary and sufficient to cause fade.

Orexin neurons regulate the sleep/wake cycle and are proposed to influence general anesthesia. In animal experiments, orexin neurons have been shown to drive emergence from general anesthesia. In human studies, however, the role of orexin neurons remains controversial, owing at least, in part, to the fact that orexin neurons are multifunctional. Orexin neurons regulate not only the sleep/wake cycle, but also body temperature. We hypothesized that orexin neurons do not directly regulate emergence from anesthesia, but instead affect emergence indirectly through thermoregulation because anesthesia-induced hypothermia can greatly influence emergence time. To test our hypothesis, we used simultaneous measurement of body temperature and locomotor activity.

We used male orexin neuron-ablated (ORX-AB) mice and their corresponding wild-type (WT) littermates to investigate the role of orexin neurons in emergence. Body temperature was recorded using an intraperitoneally implanted telemetric probe, and locomotor activity was measured using an infrared motion sensor. Induction of anesthesia and emergence from anesthesia were defined behaviorally as loss and return, respectively, of body movement. Mice received general anesthesia with 1.5% isoflurane in 100% oxygen for 30 minutes under 3 conditions. In the first experiment, the anesthesia chamber was warmed (32°C), ensuring a constant body temperature of animals during anesthesia. In the second experiment, the anesthesia chamber was maintained at room temperature (25°C), allowing body temperature to fluctuate. In the third experiment in WT mice, the anesthesia chamber was cooled (23°C) so that their body temperature would decrease to the comparable value to that obtained in the ORX-AB mice during room temperature condition.

In the warmed condition, there were no significant differences between the ORX-AB and control mice with respect to body temperature, locomotor activity, induction time, or emergence time. In the room temperature condition, however, anesthesia-induced hypothermia was greater and longer lasting in ORX-AB mice than that in WT mice. Emergence time in ORX-AB mice was significantly prolonged from the warmed condition (14.2 ± 0.8 vs 6.0 ± 1.1 minutes) whereas that in WT mice was not different (7.4 ± 0.8 vs 4.9 ± 0.2 minutes). When body temperature was decreased by cooling in WT mice, emergence time was prolonged to 12.4 ± 1.3 minutes. Induction time did not differ among temperature conditions or genotypes.

The effect of orexin deficiency to impair thermoregulation during general anesthesia is of sufficient magnitude that body temperature must be appropriately controlled when studying the role of orexin neurons in emergence from anesthesia.

In managing patients with unstable hemodynamics, monitoring cardiac output (CO) can provide critical diagnostic data. However, conventional CO measurements are invasive, intermittent, and/or inaccurate. The purpose of this study was to validate our newly developed CO monitoring system.

This system automatically determines peak velocity of the ascending aortic flow using continuous-wave Doppler transthoracic echocardiography and estimates cardiac ejection time and aortic cross-sectional area using the pulse contour of the radial arterial pressure. These parameters are continuously processed to estimate CO (CO_est). In 10 anesthetized closed-chest dogs instrumented with an aortic flowprobe to measure reference CO (CO_ref), hemodynamic conditions were varied over wide ranges by infusing cardiovascular drugs or by random atrial pacing. Under each condition, CO_ref and CO_est were determined. Absolute changes of CO_ref (CO_ref) and CO_est (CO_est), and relative changes of CO_ref (%CO_ref) and CO_est (%CO_est) from the corresponding baseline values were determined in each animal. We calibrated CO_est against CO_ref to obtain proportionally scaled CO_est (CO_est^N).

A total of 1335 datasets of CO_ref and CO_est were obtained, in which CO_ref ranged from 0.17 to 5.34 L/min. Bland–Altman analysis between CO_ref and CO_est indicated that the limits of agreement (the bias ± 1.96 x SD of the difference) and the percentage error (1.96 x [SD of the difference]/[mean CO] x 100) were from –1.01 to 1.13 L/min (95% confidence interval, –1.76 to 1.88 L/min) and 43%, respectively. The agreement between CO_ref and CO_est^N was improved, with limits of agreement from –0.53 to 0.49 L/min (95% confidence interval, –0.62 to 0.59 L/min) and the percentage error of 20%. Polar plot analysis between CO_ref and CO_est indicated that mean ± 1.96 x SD of polar angle was –2° ± 22°. Four quadrant plot analysis indicated that %CO_est correlated tightly with %CO_ref (R² = 0.93). The %CO_est and %CO_ref changed in the same direction in 95% of the datasets. Reliability of this system was well preserved under conditions of random atrial pacing and also in a continuous manner.

Over a wide range of hemodynamic conditions, irrespective of cardiac beat irregularity, this system may allow minimally invasive monitoring of CO with a good trending ability. The present results warrant further research and development of this system for future clinical application.

Inadvertent arterial placement of a large-bore catheter during attempted placement of a central venous catheter (CVC) occurs at a rate of 0.1% to 1.0% and may result in hemorrhage, pseudoaneurysm, stroke, or death. Ultrasound guidance or observation of color and pulsatility of blood are not reliable methods for avoiding this serious complication. Measurement of pressure in the needle or short plastic catheter before insertion of the guidewire has been shown to be highly reliable; however, traditional pressure measurement methodology is cumbersome. Recently a compact, sterile, single-use pressure transducer with an integrated digital display has become available. In this study, we evaluated the performance of this new device (Compass® Vascular Access).

In this prospective, observational study at 4 academic medical centers 298 CVCs were placed. Pressure was measured using the Compass transducer before and after guidewire insertion. Other details of the procedure were at the discretion of the clinician. Data describing the CVC placement and any complications were collected.

Trainees placed 279 of 298 CVCs. Ultrasound guidance was used for 286 of 298 CVCs. Seven of the CVC placements occurred in the intensive care unit, with the balance occurring in the operating room. Ten of the CVCs were placed in a subclavian vein, with the balance being internal jugular vein. Two hundred seventy-four of 298 CVCs were placed on the right side. Venous pressure measured before and after guidewire insertion was 7.2 ± 4.3 (SD) and 6.5 ± 4.3 (SD) mm Hg respectively (P = 0.03). The satisfaction score recorded by the physician performing the procedure was 8.0 ± 2.1 (SD; visual analog scale 1–10, 10 being most satisfying). There were 5 inadvertent arterial punctures (1.7%). Ultrasound guidance was used in all 5 cases of arterial puncture. All of the arterial punctures were recognized before guidewire insertion by measurement of arterial pressure with the Compass transducer. No guidewires or CVC catheters were placed in arteries.

The Compass pressure transducer for CVC placement performed as intended in 298 cases from 4 academic medical centers. There were 5 inadvertent arterial punctures despite the use of ultrasound guidance, all of which were correctly identified by pressure measurement using the Compass. The device was easily used by trainees, and users expressed a positive level of satisfaction.

Nitrous oxide (N₂O) has been widely used in clinical anesthesia for >150 years. However, use of N₂O has decreased in recent years because of concern about the drug’s metabolic side effects. But evidence that routine use of N₂O causes clinically important toxicity remains elusive. We therefore evaluated the relationship between intraoperative N₂O administration and 30-day mortality as well as a set of major inpatient postoperative complications (including mortality) in adults who had general anesthesia for noncardiac surgery.

We evaluated 49,016 patients who had noncardiac surgery at the Cleveland Clinic between 2005 and 2009. Among 37,609 qualifying patients, 16,961 were given N₂O ("nitrous," 45%) and 20,648 were not ("nonnitrous," 55%). Ten thousand seven hundred fifty-five nitrous patients (63% of the total) were propensity score-matched with 10,755 nonnitrous patients. Matched nitrous and nonnitrous patients were compared on 30-day mortality and a set of 8 in-hospital morbidity/mortality outcomes.

Inhalation of N₂O intraoperatively was associated with decreased odds of 30-day mortality (odds ratio [OR]: 97.5% confidence interval, 0.67, 0.46–0.97; P = 0.02). Furthermore, nitrous patients had an estimated 17% (OR: 0.83, 0.74–0.92) decreased odds of experiencing major in-hospital morbidity/mortality than nonnitrous (P < 0.001). Among the individual morbidities, intraoperative N₂O use was only associated with significantly lower odds of having pulmonary/respiratory morbidities (OR, 95% Bonferroni-adjusted CI: 0.59, 0.44–0.78).

Intraoperative N₂O administration was associated with decreased odds of 30-day mortality and decreased odds of in-hospital mortality/morbidity. Aside from its specific and well-known contraindications, the results of this study do not support eliminating N₂O from anesthetic practice.

In this post hoc subanalysis of the Perioperative Ischemic Evaluation (POISE) trial, we sought to determine whether nitrous oxide was associated with the primary composite outcome of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal cardiac arrest within 30 days of randomization.

The POISE trial of perioperative β-blockade was undertaken in 8351 patients. Nitrous oxide anesthesia was defined as the coadministration of nitrous oxide in patients receiving general anesthesia, with or without additional neuraxial blockade or peripheral nerve blockade. Logistic regression, with inverse probability weighting using estimated propensity scores, was used to determine the association of nitrous oxide with the primary outcome, MI, stroke, death, and clinically significant hypotension.

Nitrous oxide was administered to 1489 (29%) of the 5133 patients included in this analysis. Nitrous oxide had no significant effect on the risk of the primary outcome (112 [7.5%] vs 248 [6.9%]; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.82–1.44; 99% CI, 0.75–1.57; P = 0.58), MI (89 [6.0] vs 204 [5.6]; OR, 0.99; 95% CI, 0.75–1.31; 99% CI, 0.69–1.42; P = 0.94), stroke (6 [0.4%] vs 28 [0.8%]; OR, 0.85; 95% CI, 0.26–2.82; 99% CI, 0.17–4.11; P = 0.79), death (40 [2.7%] vs 100 [2.8%]; OR, 1.04; 95% CI, 0.6–1.81; 99% CI, 0.51–2.15; P = 0.88) or clinically significant hypotension (219 [14.7%] vs 544 [15.0%]; OR, 0.92; 95% CI, 0.74–1.15; 99% CI, 0.70–1.23; P = 0.48).

In this post hoc subanalysis, nitrous oxide was not associated with an increased risk of adverse outcomes in the POISE trial patients. This analysis was limited by the observational nature of the data and the lack of information on the concentration and duration of nitrous oxide administration. Further randomized controlled trial evidence is required.

Dexamethasone is widely used for postoperative nausea and vomiting (PONV) prophylaxis. However, there are limited data on the risk of wound complications associated with single-dose dexamethasone use for this purpose. We performed this retrospective study to determine whether intraoperative dexamethasone for PONV prevention increases the risk or severity of postoperative wound complications.

Women who underwent laparotomy for endometrial cancer between 2002 and 2007 were identified from a tumor registry. Perioperative records were reviewed to determine dexamethasone administration. Medical records were reviewed to identify wound complications including cellulitis, superficial surgical site infection, wound separation, and fascial dehiscence. Wound care needs and time to complete wound healing were compared based on dexamethasone exposure. The rate of wound complications was also compared based on dexamethasone dose. Baseline characteristics and perioperative details were evaluated for independent associations with wound complications. Logistic regression analyses were performed to predict the occurrence of wound complications.

Four hundred thirty-one patients met inclusion criteria; 192 (44.6%) received dexamethasone (4–12 mg) and 31.1% developed a wound complication. In unadjusted analysis, there was no difference in the risk of developing a wound complication based on dexamethasone exposure; 53 of 192 patients (27.6%) who received dexamethasone developed a wound complication, compared with 81 of 239 (33.9%) who did not receive dexamethasone: odds ratio (OR) (95% confidence interval [CI]) = 0.74 (0.49, 1.13), P = 0.16. There was no difference in the distribution of wound complication types based on receipt of dexamethasone (P = 0.71), or in the incidence of wound complications based on the dose of dexamethasone (P = 0.48). Of patients who developed a wound complication, there was no difference in the need for IV antibiotics, vacuum-assisted wound closure, or in the rate of fascial dehiscence based on dexamethasone exposure. The time to complete wound healing was not different between the 2 cohorts (P = 0.48). In univariate analysis, higher body mass index (BMI), higher estimated blood loss, smoking, and longer duration of surgery were predictors of wound complications. Smoking (OR [95% CI]: 2.0 [1.3, 3.2], P = 0.003) and BMI (OR [95% CI]: 1.2 [1.1, 1.3], P = 0.0003) were the only significant predictors of wound complications in the multivariate model, whereas dexamethasone remained a nonsignificant predictor (OR [95% CI]: 0.7 [0.5, 1.1], P = 0.12).

Intraoperative dexamethasone for PONV prophylaxis does not seem to increase the rate or severity of postoperative wound complications in women undergoing laparotomy for endometrial cancer. BMI and smoking were significant predictors of wound complications in this patient population.

Vascular alterations are present in pregnant women affected by preeclampsia. In this study, we assessed arterial compliance in women affected by hypertensive disorders of pregnancy. We hypothesized that arterial compliance is reduced in women affected by preeclampsia.

Forty-three hypertensive pregnant women undergoing evaluation for preeclampsia were studied. Clinical data about each patient and pregnancy were collected. Large (C1) and small (C2) artery compliance were assessed by radial tonometry, while the patients underwent laboratory tests to diagnose preeclampsia. At the time of delivery, gestational age and newborn data were recorded.

Eighteen women were diagnosed with preeclampsia. C2 levels were lower among preeclamptic versus hypertensive aproteinuric women (mean ± SD, 4.5 ± 1.3 vs 5.9 ± 2.3 mL/mm Hg · 100, P = 0.013, 95% confidence interval [CI] of difference 0.32–2.55), whereas C1 levels did not differ. In the preeclampsia group, C2 levels correlated with urine total protein concentrations measured the same day (Spearman = –0.49, P = 0.047, upper 95% CI –0.01) and with gestational age at first occurrence of hypertension (Spearman = 0.59, P = 0.010, lower 95% CI 0.17). Among singleton gestations, C2 also correlated with newborn birth weight measured at delivery (Spearman = 0.43, P = 0.009, lower 95% CI 0.11). Women who were hypertensive but aproteinuric at the time of compliance assessment, but who subsequently developed preeclampsia (n = 6), had C2 levels similar to those with an early diagnosis of preeclampsia (mean difference 0.37 mL/mm Hg · 100, 95% CI –2.42 to 1.67) and lower C2 levels than women diagnosed with gestational hypertension (P = 0.019, 95% CI 0.33–4.42 mL/mm Hg · 100).

The noninvasive assessment of arterial elasticity may contribute toward characterization of the nature of the pathophysiology in pregnancy-induced hypertensive disorders. The vascular alterations of the small arteries, as assessed by C2, may reflect the extent of vascular alterations present with preeclampsia.

Pain intensity is usually self-rated by patients with a numeric rating scale (NRS) but this scale cannot be used for noncommunicating patients. In anesthetized patients, experimental noxious stimulus increases pupillary diameter (PD) and pupillary light reflex amplitude (PLRA), the difference between PD before and after light stimulation. Labor pain is an intense acute nonexperimental stimulus, effectively relieved by epidural analgesia. In this prospective observational study, we therefore describe the effects of labor pain and pain relief with epidural analgesia on PD and PLRA, determine their association with pain intensity and determine the ability of a single measurement of PD or PLRA to assess pain.

In the first stage, pain (11-point NRS), PD, and PLRA were measured in 4 conditions in 26 laboring women: before and after epidural analgesia and in the presence and absence of a uterine contraction. Pupillometry values among the 4 conditions were compared, and the strength of the association between absolute values of pain and PD or PLRA and between pain and changes in PD or PLRA brought about by uterine contraction was assessed with r². In the second stage, 1 measurement was performed in 104 laboring women. The strength of the association between pain and PD or PLRA was assessed with r². The ability of PD or PLRA to discriminate pain (NRS > 4) was also assessed.

In the first stage, a statistically significant increase in pain, PD, and PLRA was observed during a contraction, and this change was abolished after epidural analgesia. The r² for the association between pain and changes in PD (r² = 0.25 [95% confidence interval, 0.07–0.46] or PLRA (r² = 0.34 [0.14–0.56]) brought about by a uterine contraction was higher than the r² for the association between pain and absolute values of PD (r² = 0.14 [0.04–0.28]) or PLRA (r² = 0.22 [0.10–0.37]) suggesting a stronger association for changes than for absolute values. In the second stage, r² was 0.23 [0.10–0.38] for PD and 0.26 [0.11–0.40] for PLRA and the area under the receiver operating characteristics curve was 0.82 [0.73–0.91] and 0.80 [0.71–0.89], respectively.

Changes in PD and PLRA brought about by a uterine contraction may be used as a tool to assess analgesia in noncommunicating patients.

Mutations in the ryanodine receptor type 1 gene (RYR1) that encodes the skeletal muscle–specific intracellular calcium (Ca²⁺) release channel are a cause of malignant hyperthermia (MH). In this study, we examined RYR1 mutations in a large number of North American MH-susceptible (MHS) subjects without prior genetic diagnosis.

RYR1 was examined in 120 unrelated MHS subjects from the United States in a tiered manner. The α-1 subunit of the dihydropyridine receptor gene (CACNA1S) was screened for 4 variants in subjects in whom no abnormality was found in ≥100 exons of RYR1.

Ten known causative MH mutations were found in 26 subjects. Variants of uncertain significance in RYR1 were found in 36 subjects, 16 of which are novel. Novel variants in both RYR1 and CACNA1S were found in the 1 subject who died of MH. Two RYR1 variants were found in 4 subjects. Variants of uncertain significance were found outside and inside the hotspots of RYR1. Maximal contractures in the caffeine–halothane contracture test were greater in those who had a known MH mutation or variant of uncertain significance in RYR1 than in those who did not.

The identification of novel RYR1 variants and previously observed RYR1 variants of uncertain significance in independent MHS families is necessary for demonstrating the significance of these variants for MH susceptibility and supports the need for functional studies of these variants. Continued reporting of the clinical phenotypes of MH is necessary for interpretation of genetic findings, especially because the pathogenicity of most of these genetic variants associated with MHS remains to be elucidated.

The VeinViewer (Luminetx, Memphis, TN) helps identify veins by projecting an image of subcutaneous vasculature on the skin surface. We tested the primary hypothesis that VeinViewer use improves cannulation success by skilled nurses in pediatric patients with anticipated difficult IV access. A secondary goal was to evaluate the relationship between obesity and cannulation success.

Patients aged 0 to 18 years were included. Anticipated cannulation difficulty was evaluated with the difficult IV access score. All cannulations were performed by members of the Intravenous Access Team. Patients were randomized to: (1) routine IV catheter insertion; or (2) insertion facilitated by the VeinViewer. The primary outcome was first-attempt insertion success. The proportion of successful insertions was evaluated using Cochran-Mantel-Haenszel ² analysis to adjust for any imbalanced baseline variables. The effect of obesity on cannulation success was evaluated with multivariable logistic regression.

Two hundred ninety-nine patients (49%) were randomly assigned to VeinViewer and 301 (51%) to routine cannulation. First-attempt cannulation success was 47% in patients assigned to VeinViewer vs 62% in patients assigned to routine cannulation, with an adjusted relative "risk" (95% confidence interval), of 0.76 (0.63–0.91). The Z-statistic of –3.6 crossed the "harm" boundary (Z < –2.41), with corresponding P value of 0.0003. The trial was stopped on statistical grounds since the harm boundary for the primary outcome was crossed. There was no association between first-attempt success and the 4-level categorization of obesity after adjusted for baseline variables (P = 0.94).

The VeinViewer worsened first-attempt IV insertion success by skilled nurses. Surprisingly, first-attempt success for IV cannulation was not worsened by obesity.

Up to two-thirds of patients report moderate to severe surgical site pain after craniotomy procedures, and there is understandable reluctance to manage these symptoms with systemic opioids that may impair neurological assessment. Furthermore, there is a lack of consensus and evidence concerning alternative analgesia strategies for cranial neurosurgery. Regional scalp block (RSB) is an established technique that involves infiltration of local anesthetic (LA) at well-defined anatomical sites targeting the major sensory innervation of the scalp. However, the efficacy of RSB in reducing postoperative pain remains unclear. In this study, we sought to systematically identify and review randomized controlled trials (RCTs) of RSB and synthesize an overall estimate of efficacy in a quantitative meta-analysis.

Medline, EMBASE, and the Cochrane Central Register of Controlled Trials databases were searched for all RCTs evaluating the effect of RSB on postoperative pain after craniotomy. Titles, abstracts, and papers were reviewed independently by 2 authors against predefined inclusion criteria. Two authors independently assessed the quality of included studies and extracted data on patient-reported pain scores, other analgesia requirements, and complications of RSB. Pain scores were scaled to a common 0 to 10 interval with higher scores indicating more severe pain. Meta-analysis of the pooled treatment effect was performed with a random-effects inverse-variance weighted model; heterogeneity was quantified with the I² statistic.

The literature search identified 138 unique citations, from which 7 RCTs with a total recruitment of 320 patients met the inclusion criteria. All studies used standard LA drugs (lidocaine, bupivacaine, or ropivacaine); in 3 studies, LA was combined with epinephrine. In 3 studies, RSB was performed preoperatively; in the other 4 studies, it was administered postoperatively after wound closure. No complications attributable to RSB were reported. Meta-analysis found a pooled reduction in pain score at 1 hour postoperatively (N = 5 studies; mean difference, –1.61; 95% confidence interval, –2.06 to –1.15; P < 0.001; I² = 0%). Subgroup analysis of preoperative RSB showed significant reduction in pain scores at 2, 4, and 6 to 8 hours after surgery whereas postoperative RSB was associated with significant reduction in pain scores at 2, 4, 6 to 8 and 12 hours assessments. There was also an overall reduction in the opioid requirements over the first 24 hours postoperatively, although with significant heterogeneity among the studies (N = 6 studies; standardized mean difference, –0.79; 95% confidence interval, –1.55 to –0.03; P = 0.04; I² = 86%).

Published RCTs of RSB are small and of limited methodological quality but meta-analysis shows a consistent finding of reduced postoperative pain. This evidence supports the use of RSB for patients undergoing craniotomy.

The pattern and magnitude of the hyperglycemic response to surgical stress, the added effect of low-dose steroids, and whether these differ in diabetics and nondiabetics remain unclear. We therefore tested 2 hypotheses: (1) that diabetics show a greater increase from preoperative to intraoperative glucose concentrations than nondiabetics; and (2) that steroid administration increases intraoperative hyperglycemia more so in diabetics compared with nondiabetics.

Patients scheduled for major noncardiac surgery under general anesthesia were enrolled and randomized to preoperative IV 8 mg dexamethasone or placebo, stratified by diagnosis of diabetes. Patients were part of a larger underlying trial (the Dexamethasone, Light Anesthesia and Tight Glucose Control [DeLiT] Trial). IV insulin was given when glucose concentration exceeded 215 mg/dL. The primary outcome measure was the change in glucose from the preoperative to maximal intraoperative glucose concentration. We also report the time-dependent pattern of intraoperative hyperglycemia.

Ninety patients (23% with diabetes) were randomized to dexamethasone, and 95 (29% with diabetes) were given placebo. The mean ± SD change from preoperative to maximal intraoperative glucose concentration was 63 ± 69 mg/dL in diabetics and 72 ± 45 mg/dL in nondiabetics. The mean covariable-adjusted change (95% confidence interval) in nondiabetics was 29 (13, 46) mg/dL more than in diabetics (P < 0.001). For all patients combined, mean glucose increased slightly from preoperative to incision, substantially from incision to surgery midpoint, and then remained high and fairly stable through emergence, with nondiabetic patients showing a greater increase (P < 0.001). For nondiabetics, the mean increase in glucose concentration (97.5% CI) was 29 (9, 49) mg/dL more in patients given dexamethasone than placebo (P = 0.0012). However, there was no dexamethasone effect in diabetics (P = 0.99).

Treatment of intraoperative hyperglycemia should account for the hyperglycemic surgical stress response trend depending on the stage of surgery as well as the added effects of steroid administration. Denying steroid prophylaxis for postoperative nausea and vomiting for fear of hyperglycemic response should be reconsidered given the limited effect of steroids on intraoperative blood glucose concentrations.

An alternative technique involving a "distal approach" can be used for lumbar medial branch radiofrequency denervation (LMBRFD). We described and assessed this technique by comparing it with a conventional tunnel vision approach in a prospective randomized trial.

Eighty-two patients underwent LMBRFD by a distal (n = 41) or a tunnel vision approach (n = 41). The primary end point was a comparison of the mean difference in the change of 11-point numeric rating scale (NRS) scores of low back pain from entry to the scores at 1 month (NRS at baseline—NRS at 1 month) and at 6 months (NRS at baseline—NRS at 6 months) between the distal approach group and the tunnel vision approach group. The secondary end points were a change of NRS and the Oswestry disability index over time.

Thirty-four patients in each group had complete time courses. There were no statistically significant differences in the change of NRS scores between the groups at 1 month (corrected P = 0.19; 97.5% 2-sided confidence interval [CI], –1.37 to 0.37) and 6 months (corrected P = 0.53; 97.5% CI, –1.36 to 0.77). Patients in both groups showed a statistically significant reduction in NRS and Oswestry disability index scores from baseline to that of the scores at 1 and 6 months (all P < 0.0001, Bonferroni corrected). The procedure-related pain score was significantly lower in the distal approach group (P = 0.001; 99% CI, –2.00 to –0.23).

Patients who underwent LMBRFD by the tunnel vision or distal approaches showed significant pain relief at the 6-month follow-up. Less periprocedural pain was reported in the distal approach group. We consider that the distal approach provides an improved option for LMBRFD.

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the mammalian central nervous system. GABAergic transmission has an important role in regulating nociception at the spinal dorsal horn. It is terminated by rapid uptake of the neurotransmitter from the synaptic cleft into neurons and glial cells, via specific GABA transporters (GATs). Among the 4 GATs, GAT-3 has the greatest expression in central nervous system regions closely associated with nociceptive transmission, including the spinal cord. In this study, we examined the antinociceptive effect of intrathecal administration of a selective GAT-3 inhibitor, SNAP5114, on acute, inflammatory, and neuropathic pain in experimental models.

Male Sprague-Dawley rats were used to assess thermal, mechanical, and chemical nociception in the tail flick and hotplate tests, the paw pressure test, and the formalin test. A rotarod test was performed to assess motor function. Chronic constriction injury to the sciatic nerve was induced in the rats. The electronic von Frey test and the plantar test were then performed to assess mechanical allodynia and thermal hyperalgesia. SNAP5114 (10, 50, 100, or 200 μg) was administered intrathecally to examine antinociceptive activity. To confirm whether the action of SNAP5114 was mediated by GABAergic transmission, the GABA_A receptor antagonist bicuculline (0.3 μg) or the GABA_B receptor antagonist CGP35348 (30 μg) was administered intrathecally before 200 μg of SNAP5114 in the tail flick test, the formalin test, and the electronic von Frey test.

Spinally applied SNAP5114 in normal rats dose-dependently prolonged withdrawal latencies in the tail flick test and suppressed the late-phase response in the formalin test. SNAP5114 did not affect motor performance. In the chronic constriction injury rats, SNAP5114 inhibited mechanical allodynia dose-dependently. The antinociceptive action of SNAP5114 was partially reversed by bicuculline or CGP35348 at doses at which the antagonist alone did not affect baseline behavioral responses.

These results suggest that SNAP5114 exerts antinociceptive effects by activating GABA_A and GABA_B receptors in the spinal cord. The GAT-3 inhibitor may prove useful in treatment of various painful conditions.

In this prospective, randomized, observer-blinded trial, we compared ultrasound-guided subparaneural popliteal sciatic nerve blocks performed either at or proximal to the neural bifurcation (B). We hypothesized that the total anesthesia-related time (sum of performance and onset times) would be decreased with the prebifurcation (PB) technique.

Ultrasound-guided posterior popliteal sciatic nerve block was performed in 68 patients. All subjects received an identical volume (30 mL) and mix of local anesthetic agent (1% lidocaine–0.25% bupivacaine–5 µg/mL epinephrine). In the PB group, the local anesthetic solution was deposited at the level of the common sciatic trunk, just distal to the intersection between its circular and elliptical sonographic appearances, inside the paraneural sheath. In the B group, the injection was performed inside the sheath between the tibial and peroneal divisions. A blinded observer recorded the success rate (complete tibial and peroneal sensory block at 30 minutes) and onset time. The performance time, number of needle passes, and adverse events (paresthesia, neural edema) were also recorded. All subjects were contacted 7 days after the surgery to enquire about the presence of persistent numbness or motor deficit.

Both techniques resulted in comparable success rates (85%–88%; 95% confidence interval [CI] of the intergroup difference, –14% to 19%) and required similar performance times (8.1 minutes; 95% CI of the difference, –1.65 to 1.71 minutes), onset times (15.0–17.7 minutes; 95% CI of the difference, –7.65 to 2.31 minutes), and total anesthesia-related times (23.4–26.0 minutes; 95% CI of the difference, –7.83 to 2.74 minutes). The number of needle passes and incidence of paresthesia (25%–34%) were also similar between the 2 groups. Sonographic neural swelling was detected in 2 and 3 subjects in the PB and B groups, respectively. In all 5 cases, the needle was carefully withdrawn and the injection completed uneventfully. Patient follow-up 1 week after the surgery revealed 2 patients with residual numbness. In both instances, the latter had resolved by 1 month.

When local anesthetic is injected inside the paraneural sheath, B and PB posterior popliteal sciatic nerve blocks result in comparable success and total anesthesia-related times. However, in light of the 95% CIs, we cannot exclude the possibility that an intergroup difference of 19% and 7.83 minutes might have gone undetected for success rate and total time, respectively.