The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial.

OBJECTIVES: Respiratory failure is a lethal complication of COVID-19 that has remained resistant to drug therapy. Vasoactive intestinal peptide (VIP) is shown in nonclinical studies to upregulate surfactant production, inhibit cytokine synthesis, prevent cytopathy, and block replication of the severe acute respiratory syndrome coronavirus 2 virus in pulmonary cells. The study aims to determine whether Aviptadil (synthetic VIP) can improve survival and recovery in patients with COVID-19 respiratory failure compared with placebo and demonstrate biological effects in such patients. DESIGN: A multicenter, placebo-controlled trial. SETTING: Ten U.S. hospitals: six tertiary-care hospitals and four community hospitals. PATIENTS: A total of 196 patients with COVID-19 respiratory failure. INTERVENTIONS: Participants were randomized 2:1 to receive 3 days of IV Aviptadil or placebo. MEASUREMENTS AND MAIN RESULTS: The primary end point (alive and free from respiratory failure at day 60) did not reach statistical significance (odds ratio [OR], 1.6; 95% CI, 0.86-3.11) for patients treated with Aviptadil when controlling for baseline ventilation status as prespecified in the protocol. There was, however, a statistically significant two-fold odds of improved survival (OR, 2.0; 95% CI, 1.1-3.9) at 60 days ( p = 0.035). There was significant improvement in respiratory distress ratio and reduced interleukin 6 cytokine release ( p = 0.02) by day 3.Subgroup analysis identified a statistically significant likelihood of achieving primary end point among those treated with high-flow nasal oxygen at baseline ( p = 0.039). Subjects on mechanical ventilation also experienced a 10-fold increased odds of survival with drug versus placebo ( p = 0.031). CONCLUSIONS: The primary end point did not reach statistical significance, indicating that there was no difference between Aviptadil versus placebo. However, Aviptadil improves the likelihood of survival from respiratory failure at day 60 in critical COVID-19 across all sites of care. Given the absence of drug-related serious adverse events and acceptable safety profile, we believe the benefit versus risk for the use of Aviptadil is favorable for patient treatment.

Association of Early Oxygenation Levels with Mortality in Acute Ischemic Stroke - A Retrospective Cohort Study.

BACKGROUND: Ischemic stroke is an emergency with elevated risk for morbidity and mortality. Hypoxia is harmful in acute ischemic stroke. Recent evidence raises concerns regarding hyperoxia as well in acute illness, and for supplemental oxygen therapy when SpO2greater than 92%. Current AHA/ASA guidelines recommend maintaining SpO2greater than 94%. In this study, we aimed to assess the relationship between the oxygenation levels within the first 6-hour of ischemic stroke admission and mortality. METHODS: With the approval of the Human Studies Committee (IRB #: 13.0396), we performed a retrospective cohort study of ischemic stroke patients consecutively admitted to our hospital in the years 2013-14 and 2017-18 (n = 1479). Relationship between the first 6 hours oxygenation status and in-house mortality was assessed. SpO2/FiO2 ratio was used as the oxygenation outcome parameter. Patients who were intubated at admission were excluded. Additionally, demographics, baseline confounding factors, neurological status, and laboratory values on admission were examined for their association with mortality in a multivariate logistic regression analysis. RESULTS: Mean age of patients was 64 ± 15 years. Time interval from last seen normal to hospital admission was 7 ± 5 hours (mean ± standard deviation). NIHSS on arrival was 41-9 (median-IQR). Fourteen percent of patients received IV alteplase and 6% were treated with mechanical thrombectomy. Baseline SpO2 was 97 ± 2%, and 47% of the patients required supplemental oxygen treatment per AHA/ASA guidelines. In hospital mortality rate of this cohort was 5.7%. Lower mean SpO2 /FiO2 levels were strongly correlated with increasing mortality rates (R2 = .973). Age (1.048 [1.028-1.068]), NIHSS (1.120 [1.088-1.154]), WBC (1.116 [1.061-1.175]) and Mean SpO2/FiO2 (.995 [.992-.999]) independently risk associated with mortality. CONCLUSIONS: Baseline oxygenation varies within the acute ischemic stroke patient population. In this retrospective cohort study, we are reporting a strong association between lower SpO2/FiO2 levels in the first few hours of admission and mortality. In the light of these results, we plan to prospectively assess the role of oxygenation further in the context of recanalization status of stroke.

Is video laryngoscope-assisted flexible tracheoscope intubation feasible for patients with predicted difficult airway? A prospective, randomized clinical trial.

BACKGROUND: Failed intubation may result in both increased morbidity and mortality. The combination of a video laryngoscope and a flexible tracheoscope used as a flexible video stylet may improve the success rate of securing a difficult airway. We tested the hypothesis that this combination is a feasible way to facilitate intubation in patients with a predicted difficult airway in that it will shorten intubation times and reduce the number of intubation attempts. METHODS: We conducted a randomized, prospective trial in 140 patients with anticipated difficult airways undergoing elective or urgent surgery. After insertion of video laryngoscope, patients were randomly assigned to either having their tube placed with the use of a preformed stylet (control group) or with a flexible tracheoscope (intervention group). The primary outcome measures were time to successful intubation and number of intubation attempts. RESULTS: The number of intubations requiring 2 or more intubation attempts was similar in the 2 groups (14% control vs 13% intervention, P = 1.0); the number of patients requiring 3 or more intubation attempts was not significantly different (8.6% control vs 1.4% intervention, P = 0.12). Distribution for time to intubation also did not differ between the control (median of 66 seconds, interquartile range 47-89) and the intervention group (median of 71 seconds, interquartile range 52-100; P = 0.35). In the control group, 4 patients, all with cervical spine pathology, had the trachea intubated successfully with the video laryngoscope plus flexible tracheoscope after 3 failed attempts with video laryngoscope and rigid stylet. For these 4 patients, time from the decision to change the intubation method to successful intubation with a flexible tracheoscope was 36 ± 14 seconds. Overall success probability for cervical spine patients was 100% (20/20) in the intervention group and 80% (16/20) in the control group, with an exact 95% confidence interval for the difference of 1.4% to 44%, P = 0.04. CONCLUSIONS: Flexible tracheoscope-assisted video laryngoscopic intubation is a feasible alternative to video laryngoscope only intubation in patients with predicted difficult airways. A flexible tracheoscope used in combination with video laryngoscope may also further increase the success rate of intubation in select patients with a proven difficult airway, particularly when in-line stabilization is required.

Nasopharyngeal Ventilation Compared to Facemask Ventilation: A Prospective, Randomized, Crossover Trial in Two Different Elective Cohorts.

BACKGROUND: Facemask ventilation is routinely used to preoxygenate patients before endotracheal intubation during anesthesia induction or to secure ventilation in patients with respiratory insufficiency. Occasionally, facemask ventilation cannot be performed adequately. The placement of a regular endotracheal tube through the nose into the hypopharynx may be a valid alternative to improve ventilation and oxygenation before endotracheal intubation (nasopharyngeal ventilation). We tested the hypothesis that nasopharyngeal ventilation is superior in its efficacy compared to traditional facemask ventilation. METHODS: In this prospective, randomized, crossover trial, we enrolled surgical patients requiring either nasal intubation (cohort #1, n = 20) or patients who met "difficult to mask ventilate" criteria (cohort #2, n = 20). Patients in each cohort were randomly assigned to receive pressure-controlled facemask ventilation followed by nasopharyngeal ventilation or vice versa. The ventilation settings were kept constant. The primary outcome was tidal volume. The secondary outcome was the difficulty of ventilation, measured using the Warters grading scale. RESULTS: Tidal volume was significantly increased by nasopharyngeal ventilation in cohort #1 (597 ± 156 ml vs.462 ± 220 ml, p = 0.019) and cohort #2 (525 ± 157 ml vs.259 ± 151 ml, p < 0.01). Warters grading scale for mask ventilation was 0.6 ± 1.4 in cohort #1, and 2.6 ± 1.5 in cohort #2. CONCLUSION: Patients at risk for difficult facemask ventilation may benefit from nasopharyngeal ventilation to maintain adequate ventilation and oxygenation before endotracheal intubation. This ventilation mode may offer another option for ventilation at induction of anesthesia and during the management of respiratory insufficiency, especially in the setting of "unexpected" ventilation difficulty.

Traumatic hemorrhage and chain of survival.

Trauma is the number one cause of death among Americans between the ages of 1 and 46 years, costing more than $670 billion a year. Following death related to central nervous system injury, hemorrhage accounts for the majority of remaining traumatic fatalities. Among those with severe trauma that reach the hospital alive, many may survive if the hemorrhage and traumatic injuries are diagnosed and adequately treated in a timely fashion. This article aims to review the recent advances in pathophysiology management following a traumatic hemorrhage as well as the role of diagnostic imaging in identifying the source of hemorrhage. The principles of damage control resuscitation and damage control surgery are also discussed. The chain of survival for severe hemorrhage begins with primary prevention; however, once trauma has occurred, prehospital interventions and hospital care with early injury recognition, resuscitation, definitive hemostasis, and achieving endpoints of resuscitation become paramount. An algorithm is proposed for achieving these goals in a timely fashion as the median time from onset of hemorrhagic shock and death is 2 h.

Preoperative preparation and premedication of bariatric surgical patient.

The prevalence of obesity has tripled worldwide over the past four decades. The United States has the highest rates of obesity, with 88% of the population being overweight and 36% obese. The UK has the sixth highest prevalence of obesity. The problem of obesity is not isolated to the developed world and has increasingly become an issue in the developing world as well. Obesity carries an increased risk of many serious diseases and health conditions, including type 2 diabetes, heart disease, stroke, sleep apnea, and certain cancers. Our ability to take care of this population safely throughout the perioperative period begins with a thorough and in-depth preoperative assessment and meticulous preparation. The preoperative assessment begins with being able to identify patients who suffer from obesity by using diagnostic criteria and, furthermore, being able to identify patients whose obesity is causing pathologic and physiologic changes. A detailed and thorough anesthesia assessment should be performed, and the anesthesia plan individualized and tailored to the specific patient's risk factors and comorbidities. The important components of the preoperative anesthesia assessment and patient preparation in the patient suffering from obesity include history and physical examination, airway assessment, medical comorbidities evaluation, functional status determination, risk assessment, preoperative testing, current weight loss medication, and review of any prior weight loss surgeries and their implications on the upcoming anesthetic. The preoperative evaluation of this population should occur with sufficient time before the planned operation to allow for modifications of the preoperative management without needing to delay surgery as the perioperative management of patients suffering from obesity presents significant practical and organizational challenges.

The effect of altering skin-surface cooling speeds on vasoconstriction and shivering thresholds.

BACKGROUND: Both core and skin temperatures contribute to steady-state thermoregulatory control. Dynamic thermoregulatory responses trigger aggressive defenses against rapid thermal perturbations. These responses potentially complicate interpretation of thermoregulatory studies and could slow induction of therapeutic hypothermia. We thus tested the hypothesis that rapid external skin-cooling triggers vasoconstriction and shivering at higher mean skin temperatures than slow or moderate rates of skin cooling. METHODS: Eleven healthy volunteers were cooled at 3 skin-cooling rates using forced air or/and conductive cooling in random order. One day volunteers received slow (≈2°C/h) skin cooling, and on another day, they received both medium (≈4°C/h) and fast (≈6°C/h) skin cooling. An endovascular heat-exchanging catheter maintained core temperature. Fingertip blood flow ≤0.25 mL/min defined onset of vasoconstriction; sustained ≥25% increase in oxygen consumption defined onset of shivering. Results were evaluated with repeated-measures analysis of variance, with P < 0.05 representing statistical significance. RESULTS: Volunteers were 25 ± 5 years of age (mean ± SD), 175 ± 7 cm tall, and weighed 63 ± 10 kg. Core temperature remained constant (≈37°C) throughout each study day. At vasoconstriction, mean skin temperatures were 33.2°C (95% confidence interval [CI]: 32.0°C, 34.4°C), 33.5°C (95% CI: 32.3°C, 34.7°C), and 33.0°C (95% CI: 31.4°C, 34.6°C) at slow, medium, and fast skin-cooling rates, respectively. Mean skin temperatures at shivering were also comparable: 31.4°C (95% CI: 30.3°C, 32.5°C), 31.5°C (95% CI: 30.2°C, 32.8°C), and 30.7°C (95% CI: 28.9°C, 32.5°C), respectively. CONCLUSIONS: Onset of vasoconstriction and shivering occurred at similar mean skin temperatures with all 3 cooling rates. Aggressive surface cooling can thus be used in thermoregulatory studies and for induction of therapeutic hypothermia without provoking dynamic thermoregulatory defenses.

Suppression of shivering during hypothermia using a novel drug combination in healthy volunteers.

BACKGROUND: Hypothermia may be beneficial in stroke victims; however, it provokes vigorous shivering. Buspirone and dexmedetomidine each linearly reduce the shivering threshold with minimal sedation and no respiratory depression. This study tested the hypotheses that the combination of buspirone and dexmedetomidine would (1) synergistically reduce the shivering threshold, (2) synergistically reduce the gain and maximum intensity of shivering, and (3) produce sufficient inhibition to permit cooling to 34 degrees C without excessive hypotension or sedation. METHODS: Eight healthy men were randomly assigned on 4 days to (1) no drug, (2) buspirone (60 mg orally), (3) dexmedetomidine (intravenous infusion to target plasma concentration of 0.6 ng/ml), or (4) combination of buspirone and dexmedetomidine at same doses. Lactated Ringer's solution (approximately 3 degrees C) was infused intravenously to decrease tympanic membrane temperature by 1.5 degrees C/h. Shivering threshold was defined as an increase in oxygen consumption greater than 20%. Sedation was evaluated using the Observer's Assessment of Sedation/Alertness scale. RESULTS: Mean arterial pressure and heart rate were slightly lower on dexmedetomidine and combination days. Likewise, the level of sedation was statistically different on these 2 days but clinically unimportant. Buspirone reduced the shivering threshold from 36.6 degrees C +/- 0.4 degrees C to 35.9 degrees C +/- 0.4 degrees C, dexmedetomidine reduced it to 34.7 degrees C +/- 0.5 degrees C, and the combination to 34.1 +/- 0.4 degrees C. The interaction effect of 0.04 degrees C was not significant. The gain of shivering and maximum shivering intensity were similar on each day. CONCLUSIONS: The combination of buspirone and dexmedetomidine additively reduced the shivering threshold. Thus, supplementing dexmedetomidine with buspirone blocks shivering and causes only minimal sedation.

Early Prediction of Prognosis in Elderly Acute Stroke Patients.

Acute stroke has a high morbidity and mortality in elderly population. Baseline confounding illnesses, initial clinical examination, and basic laboratory tests may impact prognostics. In this study, we aimed to establish a model for predicting in-hospital mortality based on clinical data available within 12 hours of hospital admission in elderly (≥ 65 age) patients who experienced stroke. DESIGN: Retrospective observational cohort study. SETTING: Academic comprehensive stroke center. PATIENTS: Elderly acute stroke patients-2005-2009 (n = 462), 2010-2012 (n = 122), and 2016-2017 (n = 123). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After institutional review board approval, we retrospectively queried elderly stroke patients' data from 2005 to 2009 (training dataset) to build a model to predict mortality. We designed a multivariable logistic regression model as a function of baseline severity of illness and laboratory tests, developed a nomogram, and applied it to patients from 2010 to 2012. Due to updated guidelines in 2013, we revalidated our model (2016-2017). The final model included stroke type (intracerebral hemorrhage vs ischemic stroke: odds ratio [95% CI] of 0.92 [0.50-1.68] and subarachnoid hemorrhage vs ischemic stroke: 1.0 [0.40-2.49]), year (1.01 [0.66-1.53]), age (1.78 [1.20-2.65] per 10 yr), smoking (8.0 [2.4-26.7]), mean arterial pressure less than 60 mm Hg (3.08 [1.67-5.67]), Glasgow Coma Scale (0.73 [0.66-0.80] per 1 point increment), WBC less than 11 K (0.31 [0.16-0.60]), creatinine (1.76 [1.17-2.64] for 2 vs 1), congestive heart failure (2.49 [1.06-5.82]), and warfarin (2.29 [1.17-4.47]). In summary, age, smoking, congestive heart failure, warfarin use, Glasgow Coma Scale, mean arterial pressure less than 60 mm Hg, admission WBC, and creatinine levels were independently associated with mortality in our training cohort. The model had internal area under the curve of 0.83 (0.79-0.89) after adjustment for over-fitting, indicating excellent discrimination. When applied to the test data from 2010 to 2012, the nomogram accurately predicted mortality with area under the curve of 0.79 (0.71-0.87) and scaled Brier's score of 0.17. Revalidation of the same model in the recent dataset from 2016 to 2017 confirmed accurate prediction with area under the curve of 0.83 (0.75-0.91) and scaled Brier's score of 0.27. CONCLUSIONS: Baseline medical problems, clinical severity, and basic laboratory tests available within the first 12 hours of admission provided strong independent predictors of in-hospital mortality in elderly acute stroke patients. Our nomogram may guide interventions to improve acute care of stroke.

Body temperature regulation and anesthesia.

General anesthesia is the induction and maintenance of a state of unconsciousness with the absence of pain sensation. General anesthesia is accomplished by the administration of a combination of inhaled anesthetic gases and intravenous drugs. These medications eliminate behavioral thermoregulatory compensations, leaving only autonomic defenses to offset environmental perturbations. Anesthetics inhibit thermoregulatory control in a dose-dependent fashion over the entire clinical range. Impairment of thermoregulatory control is observed by a change in thermoregulatory thresholds with the vasoconstriction threshold being affected about three times as much as the sweating threshold. Consequently, the zone between sweating and vasoconstriction thresholds, called interthreshold range, is widened dose-dependently. Impairment of thermoregulation, triggered by general anesthesia, typically causes inadvertent hypothermia. In febrile patients, general anesthesia reduces the magnitude of perioperative fever.

Temporal artery versus bladder thermometry during perioperative and intensive care unit monitoring.

BACKGROUND: Core temperature measurements are an important component of perioperative patient monitoring. It is fairly easy to obtain core temperature measurements invasively in anesthetized patients. However, such measurements are more difficult to obtain noninvasively in awake patients. Recently, a new version of a temporal artery thermometer for noninvasive core temperature measurements (TemporalScanner TAT-5000) was introduced with accuracy and precision advertised as being comparable to invasive core temperature measurements. In this study, we sought to determine if this new thermometer is an acceptable substitute for invasive bladder temperature measurement. METHODS: In 35 patients undergoing neurosurgical interventions and 35 patients in the neurosurgical intensive care unit, measurements from the temporal artery thermometer were compared with those from a bladder thermometer. Four measurements were obtained from each patient. RESULTS: Overall 280 measurement pairs were obtained. The mean bias between the methods was 0.07 degrees C +/- 0.79 degrees C; the limits of agreement were approximately 3 times greater than the a priori defined limit of +/-0.5 degrees C (-1.48 to 1.62). The sensitivity for detecting fever (core temperature >37.8 degrees C) using the temporal artery thermometer was 0.72, and the specificity was 0.97. The positive predictive value for fever was 0.89; the negative predictive value was 0.94. The sensitivity for detecting hypothermia (core temperature <35.5 degrees C) was 0.29, and the specificity was 0.95. The positive predictive value for hypothermia was 0.31, and the negative predictive value was 0.95. CONCLUSIONS: The results of this study do not support the use of temporal artery thermometry for perioperative core temperature monitoring; the temporal artery thermometer does not provide information that is an adequate substitute for core temperature measurement by a bladder thermometer.

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.

Nitrous oxide and risk of surgical wound infection: a randomised trial.

BACKGROUND: Nitrous oxide inactivates vitamin B12 and methionine synthase, thereby impairing DNA formation and, consequently, new cell formation. The gas also inhibits methionine production, which can reduce scar formation and depresses chemotactic migration by monocytes. Therefore, we assessed whether nitrous oxide increases the incidence of surgical wound infection. METHODS: We recruited 418 patients aged 18-80 years, scheduled for colon resection that was expected to last more than 2 h, at three hospitals in Austria and Hungary. Patients were randomly assigned 65% intraoperative nitrous oxide (n=208) or nitrogen (n=206), with remifentanil and isoflurane. The primary outcome was the incidence of clinical postoperative wound infection, analysed by intention to treat. FINDINGS: 206 patients in the nitrous oxide group and 202 in the nitrogen group were included in the final analysis. Duration of surgery was longer in the nitrogen group (3.4 h [1.5]) than in the nitrous oxide group (3.0 h [SD 1.3]) and arterial pressure (84 mm Hg [10] vs 81 mm Hg [9]), bispectral index values (53 [9] vs 44 [8]), and end-tidal isoflurane concentration (0.64% [0.14] vs 0.56% [0.13]) were greater in patients given nitrogen than in those given nitrous oxide. Infection rate was 15% (31/206) in patients given nitrous oxide and 20% (40/202) in those given nitrogen (p=0.205). Additionally, the ASEPSIS wound healing score, wound collagen deposition, number of patients admitted to critical care unit, time to first food ingestion, duration of hospital stay, and mortality did not differ between treatment groups. INTERPRETATION: Nitrous oxide does not increase the incidence of surgical wound infection.

Perioperative hypothermia does not enhance the risk of cancer dissemination.

BACKGROUND: Resistance to cancer metastasis is mediated by host immunity, and mild perioperative hypothermia impairs immune function. We tested the hypothesis that mild perioperative hypothermia increases the risk of cancer recurrence and subsequent mortality METHODS: In a 5- to 9-year follow-up of 140 cancer patients enrolled in a study demonstrating that 2 degrees C mild perioperative hypothermia triples wound infection risk, tumor characteristics likely to influence recurrence, patient outcome, and current health status were determined. Primary outcomes were tumor recurrence and all-cause mortality. RESULTS: Tumor status in the groups was similar and included Duke's and TNM classifications, preoperative carcinoembryonic antigen concentration, histologic differentiation, numbers of nodes biopsied and positive nodes, blood vessel invasion, and adhesion of tumor to adjacent organs. Cancer-free and overall survival rates were similar in normothermic and hypothermic patients. These data provide 80% power for detecting a 25% difference between the groups. CONCLUSIONS: Mild perioperative hypothermia did not increase recurrent tumors, cancer death, or all-cause mortality.

Dexmedetomidine and meperidine additively reduce the shivering threshold in humans.

BACKGROUND AND PURPOSE: Hypothermia might prove to be therapeutically beneficial in stroke victims; however, even mild hypothermia provokes vigorous shivering. Meperidine and dexmedetomidine each linearly reduce the shivering threshold (triggering core temperature) with minimal sedation. We tested the hypothesis that meperidine and dexmedetomidine synergistically reduce the shivering threshold without producing substantial sedation or respiratory depression. METHODS: We studied 10 healthy male volunteers (18 to 40 years) on 4 days: (1) control (no drug); (2) meperidine (target plasma level 0.3 microg/mL); (3) dexmedetomidine (target plasma level 0.4 ng/mL); and (4) meperidine plus dexmedetomidine (target plasma levels of 0.3 microg/mL and 0.4 ng/mL, respectively). Lactated Ringer's solution (approximately 4 degrees C) was infused through a central venous catheter to decrease tympanic membrane temperature by approximately 2.5 degrees C/h; mean skin temperature was maintained at 31 degrees C. An increase in oxygen consumption >25% of baseline identified the shivering threshold. Sedation was evaluated by using the Observer's Assessment of Sedation/Alertness scale. Two-way repeated-measures ANOVA was used to identify interactions between drugs. Data are presented as mean+/-SD; P<0.05 was statistically significant. RESULTS: The shivering thresholds on the study days were as follows: control, 36.7+/-0.3 degrees C; dexmedetomidine, 36.0+/-0.5 degrees C (P<0.001 from control); meperidine, 35.5+/-0.6 degrees C (P<0.001); and meperidine plus dexmedetomidine, 34.7+/-0.6 degrees C (P<0.001). Although meperidine and dexmedetomidine each reduced the shivering threshold, their interaction was not synergistic but additive (P=0.19). There was trivial sedation with either drug alone or in combination. Respiratory rate and end-tidal Pco2 were well preserved on all days. CONCLUSIONS: Dexmedetomidine and meperidine additively reduce the shivering threshold; in the small doses tested, the combination produced only mild sedation and no respiratory toxicity.

Undetected hypoglycemia in a patient receiving TPN.

CASE REPORT: A 58-year-old female was admitted to the hospital in a severely malnourished state. She was treated for Crohn's disease with total parental nutrition (TPN). The patient's blood glucose was monitored by point of care (POC) testing every 4h, and a specimen is also drawn daily for metabolic assessment. The POC blood glucose values were consistently much higher than the lab values. Humalog insulin (5 U) was given to the patient to decrease high blood glucose levels that developed following administration of TPN. The patient then became hypoglycemic as a result of this insulin treatment. POC glucose testing, performed every 4h, did not detect the iatrogenic hypoglycemia, while lab glucose results were not given close attention. The lab sample was always drawn 1-2h after insulin was given to the patient and resulted in a lower blood glucose value. In addition, the symptoms of hypoglycemia such as shaking and dizziness were masked by the patient's poor health status, supine position, and the continuously given TPN. CONCLUSIONS: These findings highlighted the importance of the correct sampling time following insulin administration and the consideration of the lab results in addition to POC. The patient's insulin regimen was modified to prevent further hypoglycemic events.

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.