Consequences of preoperative cardiac stress testing-A cohort study.

OBJECTIVE: To understand the consequences of functional cardiac stress testing among patients considering noncardiac nonophthalmologic surgery. DESIGN: A retrospective cohort study of 118,552 patients who made 159,795 visits to a dedicated preoperative risk assessment and optimization clinic between 2008 and 2018. SETTING: A large integrated health system. PATIENTS: Patients who visited a dedicated preoperative risk assessment and optimization clinic before noncardiac nonophthalmologic surgery. MEASUREMENTS: To assess changes to care delivered, we measured the probability of completing additional cardiac testing, cardiac surgery, or noncardiac surgery. To assess outcomes, we measured time-to-mortality and total one-year mortality. MAIN RESULTS: In causal inference models, preoperative stress testing was associated with increased likelihood of coronary angiography (relative risk: 8.6, 95% CI 6.1-12.1), increased likelihood of percutaneous coronary intervention (RR: 4.1, 95% CI: 1.8-9.2), increased likelihood of cardiac surgery (RR: 6.8, 95% CI 4.9-9.4), decreased likelihood of noncardiac surgery (RR: 0.77, 95% CI 0.75-0.79), and delayed noncardiac surgery for patients completing noncardiac surgery (mean 28.3 days, 95% CI: 23.1-33.6). The base rate of downstream cardiac testing was low, and absolute risk increases were small. Stress testing was associated with higher mortality in unadjusted analysis but was not associated with mortality in causal inference analyses. CONCLUSIONS: Preoperative cardiac stress testing likely induces coronary angiography and cardiac interventions while decreasing use of noncardiac surgery and delaying surgery for patients who ultimately proceed to noncardiac surgery. Despite changes to processes of care, our results do not support a causal relationship between stress testing and postoperative mortality. Analyses of care cascades should consider care that is avoided or substituted in addition to care that is induced.

Percutaneous Neuromodulation of the Brachial Plexus and Sciatic Nerve for the Treatment of Acute Pain Following Surgery: Secondary Outcomes From a Multicenter, Randomized, Controlled Pilot Study.

OBJECTIVES: We recently reported that percutaneous peripheral nerve stimulation (PNS or "neuromodulation") decreased pain and opioid consumption within the first two weeks following ambulatory surgery. However, the anatomic lead locations were combined for the analysis, and benefits for each location remain unknown. We therefore now report the effects of percutaneous PNS for brachial plexus and sciatic nerve leads separately. MATERIALS AND METHODS: Before surgery, leads were implanted percutaneously to target the brachial plexus (N = 21) for rotator cuff repair or sciatic nerve (N = 40) for foot/ankle surgery, followed by a single injection of local anesthetic. Postoperatively, subjects were randomized in a double masked fashion to 14 days of electrical stimulation (N = 30) or sham/placebo (N = 31) using an external pulse generator. The primary outcome of interest was opioid consumption and pain scores evaluated jointly. Thus, stimulation was deemed effective if superior on either outcome and at least noninferior on the other. RESULTS: For brachial plexus leads, during the first seven postoperative days pain measured with the numeric rating scale in participants given active stimulation was a median [interquartile range] of 0.8 [0.5, 1.6] versus 3.2 [2.7, 3.5] in patients given sham (p < 0.001). For this same group, opioid consumption in participants given active stimulation was 10 mg [5, 20] versus 71 mg [35, 125] in patients given sham (p = 0.043). For sciatic nerve leads, pain scores for the active treatment group were 0.7 [0, 1.4] versus 2.8 [1.6, 4.6] in patients given sham (p < 0.001). During this same period, participants given active stimulation consumed 5 mg [0, 30] of opioids versus 40 mg [20, 105] in patients given sham (p = 0.004). Treatment effects did not differ statistically between the two locations. CONCLUSIONS: Ambulatory percutaneous PNS of both the brachial plexus and sciatic nerve is an effective treatment for acute pain free of systemic side effects following painful orthopedic surgery.

Preoperative Vitamin D Deficiency Is Associated With Postoperative Delirium in Critically Ill Patients.

INTRODUCTION: Postoperative delirium is common, with a reported incidence of 11% to 80% in critically ill patients. Delirium is an independent prognostic factor for poor hospital outcomes. Low vitamin D concentrations are associated with a decline in cognitive function. We therefore tested the hypothesis that low preoperative serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with postoperative delirium in critically ill patients. METHOD: We conducted a retrospective analysis of adults in a surgical intensive care unit for at least 48 hours immediately after non-cardiac and non-neurosurgical operations at Cleveland Clinic between 2013 and 2018. Delirium was assessed by trained nurses using CAM-ICU twice daily for the initial 5 postoperative days. Any positive value was considered evidence of delirium. We assessed the association between 25(OH)D concentrations within a year before surgery and the incidence of postoperative delirium using logistic regression, adjusted for potential confounders. A linear spline term with a knot at 30 ng/ml, the threshold for normal 25(OH)D concentration, was added to accommodate a nonlinear relationship between 25(OH)D concentrations and delirium. RESULTS: We included 632 patients, who had a mean (SD) 25(OH)D concentration of 25 (15) ng/ml; 55% (346/632) experienced delirium. We observed an adjusted odds ratio of 1.4 (95% CI: [1.1, 1.8], P = 0.01) for delirium per 10 ng/ml decrease in 25(OH)D concentrations when patients' 25(OH)D concentrations were less than 30 ng/ml. In patients whose 25(OH)D concentrations were at least 30 ng/ml, the adjusted odds ratio was 0.9 (95% CI: [0.7, 1.1], P = 0.36). CONCLUSION: Preoperative 25(OH)D concentrations are associated with postoperative delirium in patients whose concentrations are below the normal threshold, but not at concentrations ≥30 ng/ml. A trial will be needed to determine whether the relationship is causal, and whether vitamin D supplementation before surgery might reduce the incidence of delirium.

Percutaneous Peripheral Nerve Stimulation (Neuromodulation) for Postoperative Pain: A Randomized, Sham-controlled Pilot Study.

BACKGROUND: Percutaneous peripheral nerve stimulation is an analgesic technique involving the percutaneous implantation of a lead followed by the delivery of electric current using an external pulse generator. Percutaneous peripheral nerve stimulation has been used extensively for chronic pain, but only uncontrolled series have been published for acute postoperative pain. The current multicenter study was undertaken to (1) determine the feasibility and optimize the protocol for a subsequent clinical trial and (2) estimate the treatment effect of percutaneous peripheral nerve stimulation on postoperative pain and opioid consumption. METHODS: Preoperatively, an electrical lead was percutaneously implanted to target the sciatic nerve for major foot/ankle surgery (e.g., hallux valgus correction), the femoral nerve for anterior cruciate ligament reconstruction, or the brachial plexus for rotator cuff repair, followed by a single injection of long-acting local anesthetic along the same nerve/plexus. Postoperatively, participants were randomized to 14 days of either electrical stimulation (n = 32) or sham stimulation (n = 34) using an external pulse generator in a double-masked fashion. The dual primary treatment effect outcome measures were (1) cumulative opioid consumption (in oral morphine equivalents) and (2) mean values of the "average" daily pain scores measured on the 0 to 10 Numeric Rating Scale within the first 7 postoperative days. RESULTS: During the first 7 postoperative days, opioid consumption in participants given active stimulation was a median (interquartile range) of 5 mg (0 to 30) versus 48 mg (25 to 90) in patients given sham treatment (ratio of geometric means, 0.20 [97.5% CI, 0.07 to 0.57]; P < 0.001). During this same period, the average pain intensity in patients given active stimulation was a mean ± SD of 1.1 ± 1.1 versus 3.1 ± 1.7 in those given sham (difference, -1.8 [97.5% CI, -2.6 to -0.9]; P < 0.001). CONCLUSIONS: Percutaneous peripheral nerve stimulation reduced pain scores and opioid requirements free of systemic side effects during at least the initial week after ambulatory orthopedic surgery.

Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation: A Pragmatic Effectiveness Trial of a Nonpharmacologic Alternative for the Treatment of Postoperative Pain.

BACKGROUND: Percutaneous peripheral nerve stimulation (PNS) is an analgesic modality involving the insertion of a lead through an introducer needle followed by the delivery of electric current after needle withdrawal. This modality has been used extensively to treat chronic pain, but only small series have been published involving postoperative pain. The ultimate objective of this study is to determine the postoperative effects of percutaneous PNS following moderately to severely painful ambulatory surgery within a real-world clinical practice setting. The primary hypothesis is that surgical pain and opioid consumption during the initial 7 days after surgery will be reduced by percutaneous PNS compared with usual and customary analgesia (dual primary outcome measures). DESIGN: A multicenter pragmatic effectiveness trial. We are randomizing participants having painful orthopedic surgical procedures of the upper and lower extremity to receive 14 days of either 1) electrical stimulation or 2) sham in a double-masked fashion. End points are being assessed at various time points over 12 postoperative months. SUMMARY: The postoperative experience will be much improved if percutaneous PNS provides potent analgesia while concurrently decreasing opioid requirements following painful surgery. Because this modality can be administered for up to 60 days at home, it may provide postoperative analgesia that outlasts surgical pain yet has relatively few risks and, unlike opioids, has no systemic side effects or potential for abuse, addiction, and overdose. Percutaneous PNS has the potential to revolutionize postoperative analgesia as it has been practiced for the past century. This study will inform key stakeholders regarding an evidence-based nonpharmacologic approach to the management of postoperative pain.

Promotion of Regular Oesophageal Motility to Prevent Regurgitation and Enhance Nutrition Intake in Long-Stay ICU Patients. A Multicenter, Phase II, Sham-Controlled, Randomized Trial: The PROPEL Study.

OBJECTIVES: To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN: A multicenter randomized sham-controlled clinical trial. SETTING: Twelve ICUs in Canada. PATIENTS: We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS: Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS: The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS: Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.

Preoperative Vitamin D Concentration and Cardiac, Renal, and Infectious Morbidity after Noncardiac Surgery.

BACKGROUND: Low 25-hydroxyvitamin D is associated with cardiovascular, renal, and infectious risks. Postsurgical patients are susceptible to similar complications, but whether vitamin D deficiency contributes to postoperative complications remains unclear. We tested whether low preoperative vitamin D is associated with cardiovascular events within 30 days after noncardiac surgery. METHODS: We evaluated a subset of patients enrolled in the biobank substudy of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were at least 45 yr with at least an overnight hospitalization. Blood was collected preoperatively, and 25-hydroxyvitamin D was measured in stored samples. The primary outcome was the composite of cardiovascular events (death, myocardial injury, nonfatal cardiac arrest, stroke, congestive heart failure) within 30 postoperative days. Secondary outcomes were kidney injury and infectious complications. RESULTS: A total of 3,851 participants were eligible for analysis. Preoperative 25-hydroxyvitamin D concentration was 70 ± 30 nmol/l, and 62% of patients were vitamin D deficient. Overall, 26 (0.7%) patients died, 41 (1.1%) had congestive heart failure or nonfatal cardiac arrest, 540 (14%) had myocardial injury, and 15 (0.4%) had strokes. Preoperative vitamin D concentration was not associated with the primary outcome (average relative effect odds ratio [95% CI]: 0.93 [0.85, 1.01] per 10 nmol/l increase in preoperative vitamin D, P = 0.095). However, it was associated with postoperative infection (average relative effect odds ratio [95% CI]: 0.94 [0.90, 0.98] per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.005) and kidney function (estimated mean change in postoperative estimated glomerular filtration rate [95% CI]: 0.29 [0.11, 0.48] ml min 1.73 m per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.004). CONCLUSIONS: Preoperative vitamin D was not associated with a composite of postoperative 30-day cardiac outcomes. However, there was a significant association between vitamin D deficiency and a composite of infectious complications and decreased kidney function. While renal effects were not clinically meaningful, the effect of vitamin D supplementation on infectious complications requires further study.

Heating and Cooling Rates With an Esophageal Heat Exchange System.

BACKGROUND: The Esophageal Cooling Device circulates warm or cool water through an esophageal heat exchanger, but warming and cooling efficacy in patients remains unknown. We therefore determined heat exchange rates during warming and cooling. METHODS: Nineteen patients completed the trial. All had general endotracheal anesthesia for nonthoracic surgery. Intraoperative heat transfer was measured during cooling (exchanger fluid at 7°C) and warming (fluid at 42°C). Each was evaluated for 30 minutes, with the initial condition determined randomly, starting at least 40 minutes after induction of anesthesia. Heat transfer rate was estimated from fluid flow through the esophageal heat exchanger and inflow and outflow temperatures. Core temperature was estimated from a zero-heat-flux thermometer positioned on the forehead. RESULTS: Mean heat transfer rate during warming was 18 (95% confidence interval, 16-20) W, which increased core temperature at a rate of 0.5°C/h ± 0.6°C/h (mean ± standard deviation). During cooling, mean heat transfer rate was -53 (-59 to -48) W, which decreased core temperature at a rate of 0.9°C/h ± 0.9°C/h. CONCLUSIONS: Esophageal warming transferred 18 W which is considerably less than the 80 W reported with lower or upper body forced-air covers. However, esophageal warming can be used to supplement surface warming or provide warming in cases not amenable to surface warming. Esophageal cooling transferred more than twice as much heat as warming, consequent to the much larger difference between core and circulating fluid temperature with cooling (29°C) than warming (6°C). Esophageal cooling extracts less heat than endovascular catheters but can be used to supplement catheter-based cooling or possibly replace them in appropriate patients.

Continuous Adductor Canal Blocks: Does Varying Local Anesthetic Delivery Method (Automatic Repeated Bolus Doses Versus Continuous Basal Infusion) Influence Cutaneous Analgesia and Quadriceps Femoris Strength? A Randomized, Double-Masked, Controlled, Split-Body Volunteer Study.

BACKGROUND: It remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for adductor canal perineural catheters. Therefore, we tested the hypothesis that scheduled bolus administration is superior or noninferior to a continuous infusion on cutaneous knee sensation in volunteers. METHODS: Bilateral adductor canal catheters were inserted in 24 volunteers followed by ropivacaine 0.2% administration for 8 hours. One limb of each subject was assigned randomly to a continuous infusion (8 mL/h) or automated hourly boluses (8 mL/bolus), with the alternate treatment in the contralateral limb. The primary end point was the tolerance to electrical current applied through cutaneous electrodes in the distribution of the anterior branch of the medial femoral cutaneous nerve after 8 hours (noninferiority delta: -10 mA). Secondary end points included tolerance of electrical current and quadriceps femoris maximum voluntary isometric contraction strength at baseline, hourly for 14 hours, and again after 22 hours. RESULTS: The 2 administration techniques provided equivalent cutaneous analgesia at 8 hours because noninferiority was found in both directions, with estimated difference on tolerance to cutaneous current of -0.6 mA (95% confidence interval, -5.4 to 4.3). Equivalence also was found on all but 2 secondary time points. CONCLUSIONS: No evidence was found to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using an adductor canal perineural catheter at 8 mL/h decreases cutaneous sensation in the distribution of the anterior branch of the medial femoral cutaneous nerve.

Management of Central Poststroke Pain: Systematic Review of Randomized Controlled Trials.

BACKGROUND AND PURPOSE: Central poststroke pain is a chronic neuropathic disorder that follows a stroke. Current research on its management is limited, and no review has evaluated all therapies for central poststroke pain. METHODS: We conducted a systematic review of randomized controlled trials to evaluate therapies for central poststroke pain. We identified eligible trials, in any language, by systematic searches of AMED, CENTRAL, CINAHL, DARE, EMBASE, HealthSTAR, MEDLINE, and PsychINFO. Eligible trials (1) enrolled ≥10 patients with central poststroke pain; (2) randomly assigned them to an active therapy or a control arm; and (3) collected outcome data≥14 days after treatment. Pairs of reviewers, independently and in duplicate, screened titles and abstracts of identified citations, reviewed full texts of potentially eligible trials, and extracted information from eligible studies. We used a modified Cochrane tool to evaluate risk of bias of eligible studies, and collected patient-important outcomes according to recommendations by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. We conducted, when possible, random effects meta-analyses, and evaluated our certainty in treatment effects using the Grading of Recommendations Assessment, Development, and Evaluation System. RESULTS: Eight eligible English language randomized controlled trials (459 patients) tested anticonvulsants, an antidepressant, an opioid antagonist, repetitive transcranial magnetic stimulation, and acupuncture. Results suggested that all therapies had little to no effect on pain and other patient-important outcomes. Our certainty in the treatment estimates ranged from very low to low. CONCLUSIONS: Our findings are inconsistent with major clinical practice guidelines; the available evidence suggests no beneficial effects of any therapies that researchers have evaluated in randomized controlled trials.

Hyperinsulinemic Normoglycemia Does Not Meaningfully Improve Myocardial Performance during Cardiac Surgery: A Randomized Trial.

BACKGROUND: Glucose-insulin-potassium (GIK) administration during cardiac surgery inconsistently improves myocardial function, perhaps because hyperglycemia negates the beneficial effects of GIK. The hyperinsulinemic normoglycemic clamp (HNC) technique may better enhance the myocardial benefits of GIK. The authors extended previous GIK investigations by (1) targeting normoglycemia while administering a GIK infusion (HNC); (2) using improved echocardiographic measures of myocardial deformation, specifically myocardial longitudinal strain and strain rate; and (3) assessing the activation of glucose metabolic pathways. METHODS: A total of 100 patients having aortic valve replacement for aortic stenosis were randomly assigned to HNC (high-dose insulin with concomitant glucose infusion titrated to normoglycemia) versus standard therapy (insulin treatment if glucose >150 mg/dl). The primary outcomes were left ventricular longitudinal strain and strain rate, assessed using speckle-tracking echocardiography. Right atrial tissue was analyzed for activation of glycolysis/pyruvate oxidation and alternative metabolic pathways. RESULTS: Time-weighted mean glucose concentrations were lower with HNC (127 ± 19 mg/dl) than standard care (177 ± 41 mg/dl; P < 0.001). Echocardiographic data were adequate in 72 patients for strain analysis and 67 patients for strain rate analysis. HNC did not improve myocardial strain, with an HNC minus standard therapy difference of -1.2% (97.5% CI, -2.9 to 0.5%; P = 0.11). Strain rate was significantly better, but by a clinically unimportant amount: -0.16 s (-0.30 to -0.03 s; P = 0.007). There was no evidence of increased glycolytic, pyruvate oxidation, or hexosamine biosynthetic pathway activation in right atrial samples (HNC, n = 20; standard therapy, 22). CONCLUSION: Administration of glucose and insulin while targeting normoglycemia during aortic valve replacement did not meaningfully improve myocardial function.

The association of serum vitamin D concentration with serious complications after noncardiac surgery.

BACKGROUND: Vitamin D deficiency is a global health problem. Epidemiological studies demonstrate that vitamin D is both cardioprotective and neuroprotective. Vitamin D also plays a substantial role in innate and acquired immunity. Our goal was to evaluate the association of serum vitamin D concentration on serious postoperative complications and death in noncardiac surgical patients. METHODS: We retrospectively analyzed the data of 3509 patients who had noncardiac surgery at the Cleveland Clinic Main Campus and had a serum vitamin D measurement. The relationship between serum vitamin D concentration and all-cause in-hospital mortality, in-hospital cardiovascular morbidity, and serious in-hospital infections was assessed as a common effect odds ratio (OR) by using a multivariate generalized estimating equation model with adjustment for demographic, medical history variables, and type and duration of surgery. RESULTS: Higher vitamin D concentrations were associated with decreased odds of in-hospital mortality/morbidity (P = 0.003). There was a linear reduction of the corresponding common effect odds ratio (OR 0.93, 95% confidence interval, 0.88-0.97) for severe in-hospital outcomes for each 5 ng/mL increase in vitamin D concentration over the range from 4 to 44 ng/mL. In addition, we found that the odds versus patients with vitamin D <13 ng/mL (i.e., 1st quintile) were significantly lower in patients with vitamin D 13-20, 20-27, 27-36, and > 36 ng/mL (i.e., 2nd-5th quintiles); the corresponding estimated ORs were 0.65 (99% confidence interval, 0.43-0.98), 0.53 (0.35-0.80), 0.44 (0.28-0.70), and 0.49 (0.31-0.78), respectively. However, there was no statistically significant difference among individual quintiles >13 ng/mL. CONCLUSIONS: Vitamin D concentrations were associated with a composite of in-hospital death, serious infections, and serious cardiovascular events in patients recovering from noncardiac surgery. While causality cannot be determined from our retrospective analysis, the association suggests that a large randomized trial of preoperative vitamin D supplementation and postoperative outcomes is warranted.

A randomized, double-blind comparison of licorice versus sugar-water gargle for prevention of postoperative sore throat and postextubation coughing.

BACKGROUND: One small study suggests that gargling with licorice before induction of anesthesia reduces the risk of postoperative sore throat. Double-lumen tubes are large and thus especially likely to provoke sore throats. We therefore tested the hypothesis that preoperative gargling with licorice solution prevents postoperative sore throat and postextubation coughing in patients intubated with double-lumen tubes. METHODS: We enrolled 236 patients having elective thoracic surgery who required intubation with a double-lumen endotracheal tube. Patients were randomly assigned to gargle 5 minutes before induction of anesthesia for 1 minute with: (1) Extractum Liquiritiae Fluidum (licorice 0.5 g); or (2) Sirupus Simplex (sugar 5 g); each diluted in 30 mL water. Sore throat and postextubation coughing were evaluated 30 minutes, 90 minutes, and 4 hours after arrival in the postanesthesia care unit, and the first postoperative morning using an 11-point Likert scale by an investigator blinded to treatment. RESULTS: The incidence of postoperative sore throat was significantly reduced in patients who gargled with licorice rather than sugar-water: 19% and 36% at 30 minutes, 10% and 35% at 1.5 hours, and 21% and 45% at 4 hours, respectively. The corresponding estimated treatment effects (relative risks) were 0.54 (95% CI, 0.30-0.99, licorice versus sugar-water; P = 0.005), 0.31 (0.14-0.68) (P < 0.001), and 0.48 (0.28-0.83) (P < 0.001). CONCLUSION: Licorice gargling halved the incidence of sore throat. Preinduction gargling with licorice appears to be a simple way to prevent a common and bothersome complication.

Bispectral index dynamics during propofol hypnosis is similar in red-haired and dark-haired subjects.

BACKGROUND: We have previously shown that red hair is associated with increased desflurane requirement for immobility, compared with dark hair. The effect of red hair on IV anesthetic requirement remains unknown. We tested the hypothesis that the propofol concentration in the effect site associated with half maximal electroencephalogram response, Ce50, is at least 50% higher in subjects with red hair. METHODS: We modeled the propofol concentration versus electroencephalogram response relationship using a 2-step approach in 29 healthy dark- and red-haired volunteers receiving a propofol infusion to produce loss of consciousness. Bispectral Index (BIS) was the measure of drug effect. The parameters of a 3-compartment pharmacokinetic model were fit to measured arterial propofol concentrations. The relationship between effect-site propofol concentration (Ce) and BIS was characterized using a sigmoid Emax model. Model performance and accuracy of the estimated parameters were evaluated using accepted metrics and bootstrap resampling. The effect of hair color on the Ce50 for BIS response in the final model was assessed using a threshold of 6.63 (P<0.01) in reduction of -2 log likelihood. The influence of body weight on the model was also assessed. RESULTS: The inclusion of hair color as a model covariate did not improve either the pharmacokinetic or the pharmacodynamic model. A separate analysis for the dark- and red-haired subjects estimated a median (95% confidence interval) Ce50 BIS of 2.71 µg/mL (2.28-3.36 µg/mL) and 2.57 µg/mL (1.68-3.60 µg/mL), respectively. Body weight was a significant covariate for the CL1 and V1. CONCLUSIONS: Red hair phenotype does not affect the pharmacokinetics or pharmacodynamics of propofol.

Erythrocyte storage duration is not associated with increased mortality in noncardiac surgical patients: a retrospective analysis of 6,994 patients.

BACKGROUND: More than 5 million patients receive erythrocyte transfusions in the United States every year. Previous studies linked the storage duration of allogeneic erythrocytes to the risk of severe postoperative complications, especially after cardiac or trauma surgery. Limited data are available for noncardiac surgical patients. We therefore evaluated the association between storage duration of transfused erythrocytes and postoperative all-cause mortality among general surgery patients. METHODS: Perioperative data corresponding to 63,319 adult, general surgery patients were obtained from our registry and merged with blood product data. Patients receiving solely leukocyte-reduced, allogeneic erythrocyte transfusions were included. Multivariable Cox proportional hazards regression was used to characterize the relationship between median erythrocyte storage duration and postoperative mortality rate, adjusting for characteristics plausibly influencing the storage duration of erythrocytes. RESULTS: Of the 6,994 patients included in the final analysis, 23, 44, 11, 9, and 13% received 1, 2, 3, 4, and ≥5 erythrocyte units, respectively. The authors found no evidence that increasing median storage duration was associated with a difference in the risk of postoperative mortality (hazard ratio, 0.99 [0.94-1.04]; P = 0.64). Analyzing the mean storage duration of erythrocyte units as a function of year of transfusion, the authors demonstrate a relevant decrease in utilization of the oldest blood units, whereas young blood storage duration remains nearly unchanged. CONCLUSION: The authors' study supports the recent literature in surgical and medical patients and underlines the importance of sufficiently powered randomized trials to finally resolve the erythrocyte storage duration debate.

Blood storage duration and biochemical recurrence of cancer after radical prostatectomy.

OBJECTIVE: To test the hypothesis that perioperative transfusion of allogeneic and autologous red blood cells (RBCs) stored for a prolonged period speeds biochemical recurrence of prostate cancer after prostatectomy. PATIENTS AND METHODS: We evaluated biochemical prostate cancer recurrence in men who had undergone radical prostatectomy and perioperative blood transfusions from July 6, 1998, through December 27, 2007. Those who received allogeneic blood transfusions were assigned to nonoverlapping "younger," "middle," and "older" RBC storage duration groups. Those who received autologous RBC transfusions were analyzed using the maximum storage duration as the primary exposure. We evaluated the association between RBC storage duration and biochemical recurrence using multivariable Cox proportional hazards regression. RESULTS: A total of 405 patients received allogeneic transfusions. At 5 years, the biochemical recurrence-free survival rate was 74%, 71%, and 76% for patients who received younger, middle, and older RBCs, respectively; our Cox model indicated no significant differences in biochemical recurrence rates between the groups (P=.82; Wald test). Among patients who received autologous transfusions (n=350), maximum RBC age was not significantly associated with biochemical cancer recurrence (P=.95). At 5 years, the biochemical recurrence-free survival rate was 85% and 81% for patients who received younger and older than 21-day-old RBCs, respectively. CONCLUSION: In patients undergoing radical prostatectomy who require RBC transfusion, recurrence risk does not appear to be independently associated with blood storage duration.

Spinal cord stimulation for chronic visceral abdominal pain.

BACKGROUND: Spinal cord stimulation (SCS) may reduce pain scores and improve function in patients with chronic visceral abdominal pain. We thus present our large clinical experience in SCS for visceral abdominal pain. METHODS: We trialed spinal cord stimulation in 35 patients, each of whom was shown by retrograde differential epidural block to have either visceral pain (n = 32) or mixed visceral and central pain (n = 3). SCS trials lasted 4 to 14 days (median 9 days). SCS lead tips were mostly positioned at T5 (n = 11) or T6 (n = 10). RESULTS: Thirty patients (86%) reported at least 50% pain relief upon completion of the trial. Among these, pretrial visual analog scale (VAS) pain scores averaged 8.2 +/- 1.6 (SD) and opioid use averaged 110 +/- 119 mg morphine sulfate equivalents. During the trial, VAS pain scores decreased to 3.1 +/- 1.6 cm (P < 0.001, Mann-Whitney Rank Sum Test) and opioid use decreased to 70 +/- 68 mg morphine equivalent a day (P = 0.212). Five patients failed the trial, one was lost to follow-up, and 19 were followed for the whole year. Seven patients were either followed for less than a year (n = 3) or the SCS system was removed due to infection or lead migration (n = 4). One patient despite the successful trial felt no improvements at 6 months after the implant and requested an explant of the SCS device. Among the 28 patients who received permanent implant, 19 were followed at least a year. Their VAS pain scores remained low (3.8 +/- 1.9 cm; P < 0.001) at 1 year, as did opioid use (38 +/- 48 mg morphine equivalents; P = 0.089). CONCLUSIONS: Spinal cord stimulation may be a useful therapeutic option for patients with severe visceral pain.

Listening to music during anesthesia does not reduce the sevoflurane concentration needed to maintain a constant bispectral index.

BACKGROUND: Music reduces stress responses in awake subjects. However, there remains controversy about the role of music or therapeutic suggestions during general anesthesia and postoperative recovery. We thus tested the hypothesis that intraoperative exposure to soothing music reduces the end-tidal concentration of sevoflurane (ETSevo) necessary to maintain bispectral index (BIS) near 50 during laparoscopic surgery. METHODS: Forty patients, aged 40-60 yrs, ASA I and II, undergoing laparoscopic hernias or cholecystectomy under general anesthesia were studied. All patients were connected to a BIS monitor. Anesthesia was induced with fentanyl 2 microg/kg, sevoflurane in oxygen, rocuronium (0.6 mg/kg), and maintained with sevoflurane in oxygen and 50% nitrous oxide, with an infusion of fentanyl (1 microg x kg(-1) x h(-1)). Sevoflurane was titrated to maintain BIS near 50 throughout the procedure. Patients were randomly assigned to either listen to music or not. RESULTS: The ETSevo necessary to maintain a BIS near 50 was virtually identical in patients who listened to music (1.29 +/- 0.33%) and those who did not (1.27 +/- 0.33%, P = 0.84). Patients who listened to music reported slightly less pain, but the difference was not statistically significant. Mean arterial blood pressure was slightly higher in patients who listened to music (101 +/- 11 mm Hg) than in those who did not (94 +/- 10 mm Hg, P = 0.040). CONCLUSIONS: The end-tidal concentration of sevoflurane required to maintain BIS near 50 during laparoscopic cholecystectomy was virtually identical in patients exposed to music or not. Although previous work suggests that music reduces preoperative stress and may be useful during sedation, our results do not support the use of music during surgery.

Differential effects of antibiotics in combination with G-CSF on survival and polymorphonuclear granulocyte cell functions in septic rats.

BACKGROUND: In addition to their antimicrobial activity, antibiotics modulate cellular host defence. Granulocyte-colony stimulating factor (G-CSF) is also a well known immunomodulator; however little is known about the interactions of G-CSF with antibiotics. We investigated in septic rats the effects of two antibiotic combinations with G-CSF. METHODS: In two clinic modelling randomised trials (CMRTs), male Wistar rats were anesthetized, given antibiotic prophylaxis, had a laparotomy with peritoneal contamination and infection (PCI), and were randomly assigned (n = 18 rats/group) to: 1) PCI only; 2) PCI+antibiotic; and, 3) PCI+antibiotic+G-CSF prophylaxis (20 mug/kg, three times). This sequence was conducted first with 10 mg/kg coamoxiclav, and then with ceftriaxone/metronidazole (Cef/met, 10/3 mg/kg). In additional animals, the blood cell count, migration and superoxide production of PMNs, systemic TNF-alpha and liver cytokine mRNA expression levels were determined. RESULTS: Only the combination coamoxiclav plus G-CSF improved the survival rate (82 vs. 44%, p < 0.001). Improved survival with this combination was accompanied by normalised antimicrobial PMN migratory activity and superoxide production, along with normalised systemic TNF-alpha levels and a reduced expression of TNF-alpha and IL-1 in the liver. CONCLUSION: There are substantial differences in the interaction of antibiotics with G-CSF. Therefore, the selection of the antibiotic for combination with G-CSF in sepsis treatment should be guided not only by the bacteria to be eliminated, but also by the effects on antimicrobial functions of PMNs and the cytokine response.

New circulating-water devices warm more quickly than forced-air in volunteers.

BACKGROUND: Newer circulating-water systems supply more heat than forced-air, mainly because the heat capacity of water is much greater than for that of dry warm air and, in part, because they provide posterior as well as anterior heating. Several heating systems are available, but three major ones have yet to be compared directly. We therefore compared two circulating-water systems with a forced-air system during simulation of upper abdominal or chest surgery in volunteers. METHODS: Seven healthy volunteers participated on three separate study days. Each day, they were anesthetized and cooled to a core temperature near 34 degrees C, which was maintained for 45-60 min. They were then rewarmed with one of three warming systems until distal esophageal core temperature reached 36 degrees C or anesthesia had lasted 8 h. The warming systems were 1) energy transfer pads (two split torso pads and two universal pads; Kimberly Clark, Roswell, GA); 2) circulating-water garment (Allon MTRE 3365 for cardiac surgery, Akiva, Israel); and 3) lower body forced-air warming (Bair Hugger #525, #750 blower, Eden Prairie, MN). Data are presented as mean +/- sd; P < 0.05 was statistically significant. RESULTS: The rate of increase of core temperature from 34 degrees C to 36 degrees C was 1.2 degrees C +/- 0.2 degrees C/h with the Kimberly Clark system, 0.9 degrees C +/- 0.2 degrees C/h with the Allon system, and 0.6 degrees C +/- 0.1 degrees C/h with the Bair Hugger (P = 0.002). CONCLUSIONS: The warming rate with the Kimberly Clark system was 25% faster than with the Allon system and twice as fast as with the Bair Hugger. Both circulating-water systems thus warmed hypothermic volunteers in significantly less time than the forced-air system.