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1.  Perioperative Glucose Control in Neurosurgical Patients 
Many neurosurgery patients may have unrecognized diabetes or may develop stress-related hyperglycemia in the perioperative period. Diabetes patients have a higher perioperative risk of complications and have longer hospital stays than individuals without diabetes. Maintenance of euglycemia using intensive insulin therapy (IIT) continues to be investigated as a therapeutic tool to decrease morbidity and mortality associated with derangements in glucose metabolism due to surgery. Suboptimal perioperative glucose control may contribute to increased morbidity, mortality, and aggravate concomitant illnesses. The challenge is to minimize the effects of metabolic derangements on surgical outcomes, reduce blood glucose excursions, and prevent hypoglycemia. Differences in cerebral versus systemic glucose metabolism, time course of cerebral response to injury, and heterogeneity of pathophysiology in the neurosurgical patient populations are important to consider in evaluating the risks and benefits of IIT. While extremes of glucose levels are to be avoided, there are little data to support an optimal blood glucose level or recommend a specific use of IIT for euglycemia maintenance in the perioperative management of neurosurgical patients. Individualized treatment should be based on the local level of blood glucose control, outpatient treatment regimen, presence of complications, nature of the surgical procedure, and type of anesthesia administered.
PMCID: PMC3286889  PMID: 22400022
2.  Estimation of Mean-body Temperature From Mean-skin and Core Temperature 
Anesthesiology  2006;105(6):1117-1121.
Background: Mean-body temperature (MBT) is the mass-weighted average temperature of body tissues. Core temperature is easy to measure, but direct measurement of peripheral tissue temperature is painful, risky, and requires complex calculations. Alternatively MBT can be estimated from core and mean skin temperatures with a formula proposed by Burton in 1935: MBT = 0.64. TCore + 0.36. TSkin. This formula remains widely used, but not been validated in the perioperative period and seems unlikely to remain accurate in dynamic perioperative conditions such as cardiopulmonary bypass. We thus tested the hypothesis that MBT, as estimated with Burton’s formula, poorly estimates measured MBT at a temperature range between 18 and 36.5° C.
Materials and Methods: We re-evaluated four of our previously published studies in which core and mass-weighted mean peripheral tissue temperatures were measured in patients undergoing substantial thermal perturbations. Peripheral compartment temperatures were estimated using fourth-order regression and integration over volume from 18 intramuscular needle thermocouples, 9 skin temperatures, and "deep" hand and foot temperature. MBT was determined from mass-weighted average of core and peripheral tissue temperatures and estimated from core temperature and mean skin temperature (15 area-weighted sites) using Burton’s formula.
Results: 913 data pairs from 44 study subjects were included in the analysis. Measured MBT ranged from 18 to 36.5°C. There was a remarkably good relationship between measured and estimated MBT: MBTmeasured = 0.94 · MBTestimated + 2.15, r2 = 0.98. Differences between the estimated and measured values averaged -0.09 ± 0.42°C.
Conclusions: We concluded that estimation of MBT from mean skin and core temperatures is generally accurate and precise.
PMCID: PMC1752199  PMID: 17122574
3.  Doxapram Only Slightly Reduces the Shivering Threshold in Healthy Volunteers 
Anesthesia and analgesia  2005;101(5):1368-1373.
We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on two days: Control and Doxapram (intravenous infusion to a plasma concentration of 2.4 ±0.8 μg/mL, 2.5 ±0.9 μg/mL, and 2.6 ±1.1 μg/mL at the sweating, vasoconstriction, and shivering thresholds, respectively). Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the sweating, vasoconstriction, and shivering thresholds with compensation for changes in skin temperature. Data were analyzed with paired t tests and presented as means ± SDs; P < 0.05 was considered statistically significant. Doxapram did not change the sweating (Control: 37.5±0.4°C, Doxapram: 37.3±0.4°C, P=0.290) or the vasoconstriction threshold (36.8±0.7 vs. 36.4±0.5°C; P=0.110). However, it significantly reduced the shivering threshold from 36.2±0.5 to 35.7±0.7°C (P=0.012). No sedation or symptoms of panic were observed on either study day. The observed reduction in the shivering threshold explains the drug's efficacy for treatment of postoperative shivering; however, a reduction of only 0.5°C is unlikely to markedly facilitate induction of therapeutic hypothermia as a sole agent.
PMCID: PMC1552102  PMID: 16243996
Anesthesia; Hypothermia; Temperature; Thermoregulation
4.  Dantrolene Reduces the Threshold and Gain for Shivering 
Anesthesia and analgesia  2004;98(5):1318-contents.
Dantrolene is used for treatment of life-threatening hyperthermia, yet its thermoregulatory effects are unknown. We tested the hypothesis that dantrolene reduces the threshold (triggering core temperature) and gain (incremental increase) of shivering. With IRB approval and informed consent, healthy volunteers were evaluated on two random days: control and dantrolene (≈2.5 mg/kg plus a continuous infusion). In study 1, 9 men were warmed until sweating was provoked and then cooled until arterio-venous shunt constriction and shivering occurred. Sweating was quantified on the chest using a ventilated capsule. Absolute right middle fingertip blood flow was quantified using venous-occlusion volume plethysmography. A sustained increase in oxygen consumption identified the shivering threshold. In study 2, 9 men were given cold Ringer's solution IV to reduce core temperature ≈2°C/h. Cooling was stopped when shivering intensity no longer increased with further core cooling. The gain of shivering was the slope of oxygen consumption vs. core temperature regression. In Study 1, sweating and vasoconstriction thresholds were similar on both days. In contrast, shivering threshold decreased 0.3±0.3°C, P=0.004, on the dantrolene day. In Study 2, dantrolene decreased the shivering threshold from 36.7±0.2 to 36.3±0.3°C, P=0.01 and systemic gain from 353±144 to 211±93 ml·min−1·°C−1, P=0.02. Thus, dantrolene substantially decreased the gain of shivering, but produced little central thermoregulatory inhibition.
PMCID: PMC1454474  PMID: 15105208
Temperature: hyperthermia, fever; Pharmacology: dantrolene; Complications: shivering
5.  Effects of a Circulating-water Garment and Forced-air Warming on Body Heat Content and Core Temperature 
Anesthesiology  2004;100(5):1058-1064.
Background: Forced-air warming is sometimes unable to maintain perioperative normothermia. We therefore compared heat transfer, regional heat distribution, and core rewarming of forced-air warming with a novel circulating-water garment.
Methods: Nine volunteers were each evaluated on two randomly ordered study days. They were anesthetized and cooled to a core temperature near 34°C. The volunteers were subsequently warmed for 2.5 hours with either a circulating-water garment or forced-air cover. Overall, heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Average arm and leg (peripheral) tissue temperatures were determined from 18 intramuscular needle thermocouples, 15 skin thermal flux transducers, and “deep” arm and foot thermometers.
Results: Heat production (≈ 60 kcal/h) and loss (≈45 kcal/h) were similar with each treatment before warming. The increase in heat transfer across anterior portions of the skin surface was similar with each warming system (≈65 kcal/h). Forced-air warming had no effect on posterior heat transfer whereas circulating-water transferred 21 ± 9 kcal/h through the posterior skin surface after a half hour of warming. Over 2.5 h, circulating-water thus increased body heat content 56% more than forced air. Core temperatures thus increased faster than with circulating water than forced air, especially during the first hour, with the result that core temperature was 1.1 ± 0.7°C greater after 2.5 h (P < 0.001). Peripheral tissue heat content increased twice as much as core heat content with each device, but the core-to-peripheral tissue temperature gradient remained positive throughout the study.
Conclusions: The circulating-water system transferred more heat than forced air, with the difference resulting largely from posterior heating. Circulating water rewarmed patients 0.4°C/h faster than forced air. A substantial peripheral-to-core tissue-temperature gradient with each device indicated that peripheral tissues insulated the core, thus slowing heat transfer.
PMCID: PMC1409744  PMID: 15114200
6.  The New Perilaryngeal Airway (CobraPLA™)1 Is as Efficient as the Laryngeal Mask Airway (LMA™)2, But Provides Better Airway Sealing Pressures 
Anesthesia and analgesia  2004;99(1):272-278.
The Laryngeal Mask Airway (LMA) is a frequently-used efficient airway device, yet it sometimes seals poorly, thus reducing the efficacy of positive-pressure ventilation. The Perilaryngeal Airway (CobraPLA) is a novel airway device with a larger pharyngeal cuff (when inflated). We tested the hypothesis that the CobraPLA was superior to LMA with regard to insertion time and airway sealing pressure and comparable to LMA in airway adequacy and recovery characteristics. After midazolam and fentanyl, 81 ASA I-II outpatients having elective surgery were randomized to receive an LMA or CobraPLA. Anesthesia was induced with propofol (2.5 mg/kg, IV), and the airway inserted. We measured 1) insertion time; 2) adequacy of the airway (no leak at 15-cm-H2O peak pressure or tidal volume of 5 ml/kg); 3) airway sealing pressure; 4) number of repositioning attempts; and 5) sealing quality (no leak at tidal volume of 8 ml/kg). At the end of surgery, gastric insufflation, postoperative sore throat, dysphonia, and dysphagia were evaluated. Data were compared with unpaired t-tests, chi-square tests, or Fisher’s Exact tests; P<0.05 was significant. Patient characteristics, insertion times, airway adequacy, number of repositioning attempts, and recovery were similar in each group. Airway sealing pressure was significantly greater with CobraPLA (23±6 cm H2O) than LMA (18±5 cm H2O, P<0.001). The CobraPLA has insertion characteristics similar to LMA, but better airway sealing capabilities.
PMCID: PMC1364541  PMID: 15281543
Airway: Sealing. Cuff Pressure. Insertion. Leak. Pharynx; Equipment: Laryngeal mask airway. Perilaryngeal airway; Ventilation: Controlled. Spontaneous; Anesthesia
7.  Magnesium Sulfate Only Slightly Reduces the Shivering Threshold in Humans 
British journal of anaesthesia  2005;94(6):756-762.
Background: Hypothermia may be an effective treatment for stroke or acute myocardial infarction; however, it provokes vigorous shivering, which causes potentially dangerous hemodynamic responses and prevents further hypothermia. Magnesium is an attractive antishivering agent because it is used for treatment of postoperative shivering and provides protection against ischemic injury in animal models. We tested the hypothesis that magnesium reduces the threshold (triggering core temperature) and gain of shivering without substantial sedation or muscle weakness.
Methods: We studied nine healthy male volunteers (18-40 yr) on two randomly assigned treatment days: 1) Control and 2) Magnesium (80 mg·kg-1 followed by infusion at 2 g·h-1). Lactated Ringer's solution (4°C) was infused via a central venous catheter over a period of approximately 2 hours to decrease tympanic membrane temperature ≈1.5°C·h-1. A significant and persistent increase in oxygen consumption identified the threshold. The gain of shivering was determined by the slope of oxygen consumption vs. core temperature regression. Sedation was evaluated using verbal rating score (VRS, 0-10) and bispectral index of the EEG (BIS). Peripheral muscle strength was evaluated using dynamometry and spirometry. Data were analyzed using repeated-measures ANOVA; P<0.05 was statistically significant.
Results: Magnesium reduced the shivering threshold (36.3±0.4 [mean±SD] vs. 36.6±0.3°C, P=0.040). It did not affect the gain of shivering (Control: 437±289, Magnesium: 573±370 ml·min-1·°C-1, P=0.344). The magnesium bolus did not produce significant sedation or appreciably reduce muscle strength.
Conclusions: Magnesium significantly reduced the shivering threshold; however, due to the modest absolute reduction, this finding is considered to be clinically unimportant for induction of therapeutic hypothermia.
PMCID: PMC1361806  PMID: 15749735
Magnesium; Temperature; Thermoregulation; Therapeutic hypothermia; Brain protection; Cardiac protection; Shivering
8.  The Timing of Acupuncture Stimulation Does Not Influence Anesthetic Requirement 
Anesthesia and analgesia  2005;100(2):387-392.
Studies suggest that acupuncture is more effective when induced before induction of general anesthesia than afterwards. We tested the hypothesis that electro-acupuncture initiated 30 minutes before induction reduces anesthetic requirement more than acupuncture initiated after induction. Seven volunteers were each anesthetized with desflurane on 3 study days. Needles were inserted percutaneously at 4 acupuncture points thought to produce analgesia in the upper abdominal area and provide generalized sedative and analgesic effects: Zusanli (St36), Sanyinjiao (Sp6), Liangqiu (St34), and Hegu (LI4). Needles were stimulated at 2-Hz and 10-Hz, with frequencies alternating at two-second intervals. On Preinduction day, electro-acupuncture was started 30 minutes before induction of anesthesia and maintained throughout the study. On At-induction day, needles were positioned before induction of anesthesia, but electro-acupuncture stimulation was not initiated until after induction. On Control day, electrodes were positioned near the acupoints, but needles were not inserted. Noxious electrical stimulation was administered via 25-G needles on the upper abdomen (70 mA, 100 Hz, 10 seconds). Desflurane concentration was increased 0.5% when movement occurred and decreased 0.5% when it did not. These up-and-down sequences continued until volunteers crossed from movement to no-movement 4 times. The P50 of logistic regression identified desflurane requirement. Desflurane requirement was similar on the Control (5.2±0.6%, mean±SD), Preinduction (5.0±0.8%), and At-induction (4.7±0.3%, P=0.125) days. This type of acupuncture is thus unlikely to facilitate general anesthesia or decrease the need for anesthetic drugs.
PMCID: PMC1360236  PMID: 15673863
Anesthetic technique: Acupuncture, Electro-acupuncture; Potency: anesthesia requirement; Anesthetics, volatile: desflurane
9.  Cutaneous Heat Loss with Three Surgical Drapes, One Impervious to Moisture 
Anesthesia and analgesia  2005;100(3):738-contents.
A new surgical drape, which is impervious to moisture, presumably reduces evaporative heat loss. We compared cutaneous heat loss and skin temperature in volunteers covered with this drape to two conventional surgical drapes (Large Surgical Drape and Medline Proxima). With IRB approval and informed consent, we calculated cutaneous heat loss and skin-surface temperatures from 15 area-weighted thermal flux transducers in 8 volunteers. In random order, each of the drapes was evaluated with dry transducers and moistened transducers (simulating wet skin). After a 20-minute uncovered control period, volunteers were covered from the neck down for 40 minutes. Data were recorded continuously and averaged over 10-minutes. Results were similar for all three drapes for dry or moist conditions. Under dry conditions, baseline heat loss was 82±14 watts (W) and decreased 30% with a surgical drape (P<0.001). Under moist conditions, baseline heat loss was 231±45 W and decreased 29% with a drape covering (P<0.001). Moist skin increased heat loss 282% (P<0.001). There were no clinically important differences in skin temperature among the covers with dry or moist skin. Moist skin increased heat loss nearly three-fold, but there were no differences among the drapes. We conclude that loss is comparable with impervious and conventional drapes with either moist or dry skin.
PMCID: PMC1351377  PMID: 15728062
Evaporation; Heat flux; Insulation; Surgical drapes; Sweat; Temperature; Thermoregulation
10.  Local warming and insertion of peripheral venous cannulas: single blinded prospective randomised controlled trial and single blinded randomised crossover trial 
BMJ : British Medical Journal  2002;325(7361):409.
To determine whether local warming of the lower arm and hand facilitates peripheral venous cannulation.
Single blinded prospective randomised controlled trial and single blinded randomised crossover trial.
Neurosurgical unit and haematology ward of university hospital.
100 neurosurgical patients and 40 patients with leukaemia who required chemotherapy.
Neurosurgical patients' hands and forearms were covered for 15 minutes with a carbon fibre heating mitt. Patients were assigned randomly to active warming at 52°C or passive insulation (heater not activated). The same warming system was used for 10 minutes in patients with leukaemia. They were assigned randomly to active warming or passive insulation on day 1 and given alternative treatment during the subsequent visit.
Main outcome measures
Primary: success rate for insertion of 18 gauge cannula into vein on back of hand. Secondary: time required for successful cannulation.
In neurosurgical patients, it took 36 seconds (95% confidence interval 31 to 40 seconds) to insert a cannula in the active warming group and 62 (50 to 74) seconds in the passive insulation group (P=0.002). Three (6%) first attempts failed in the active warming group compared with 14 (28%) in the passive insulation group (P=0.008). The crossover study in patients with leukaemia showed that insertion time was reduced by 20 seconds (8 to 32, P=0.013) with active warming and that failure rates at first attempt were 6% with warming and 30% with passive insulation (P<0.001).
Local warming facilitates the insertion of peripheral venous cannulas, reducing both time and number of attempts required. This may decrease the time staff spend inserting cannulas, reduce supply costs, and improve patient satisfaction.
What is already known on this topicInsertion of peripheral venous cannulas may be difficult because of severe vasoconstrictionVasoconstriction can be overcome by local heatingWhat this study addsActive local warming facilitates the insertion of peripheral venous cannulas, reducing both the time and number of attempts requiredLocal warming will decrease the amount of time staff spend inserting cannulas, reduce supply costs, and improve patient satisfaction
PMCID: PMC119431  PMID: 12193353

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