Stephen M. Koch

N-acetylcysteine inhibits muscle fatigue in humans.

N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively inhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experiments test the hypothesis that NAC pretreatment can inhibit acute muscular fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in water by intravenous infusion. The subject then sat in a chair with surface electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimulated to contract electrically (40-55 mA, 0.2-ms pulses) and force production was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions (MVC) of ankle dorsiflexor muscle groups and during electrical stimulation of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1). Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subsequently were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did not alter the function of unfatigued muscle; MVC performance and the force-frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force output by approximately 15% (P < 0.0001), an effect that was evident after 3 min of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue. N-acetylcysteine pretreatment can improve performance of human limb muscle during fatiguing exercise, suggesting that oxidative stress plays a causal role in the fatigue process and identifying antioxidant therapy as a novel intervention that may be useful clinically.

Effect of passive range of motion on intracranial pressure in neurosurgical patients

PURPOSE A prospective patient study was done to evaluate the effect of passive range of motion (PROM) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in neurosurgical patients. MATERIALS AND METHODS Twelve adult patients admitted to the neurological-neurosurgical intensive care unit of a community teaching hospital were enrolled in the study. The study patients all required ICP monitoring and they underwent a total of 20 PROM sessions. Six patients (10 PROM sessions) were mechanically ventilated, and six patients (10 PROM sessions) were breathing spontaneously. Mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), and ICP were measured at baseline and at 1-minute intervals during the physical therapy session. CPP was calculated as the difference between MAP and ICP. RESULTS No significant changes were detected in MAP, ICP, HR, or RR during the study period. Calculated CPP remained unchanged. Mean duration of PROM intervention was 7 +/- 1 minute. Mean Glasgow Coma Scale (GCS) for mechanically ventilated patients was 7 +/- 1.3 and for spontaneously breathing patients 13 +/- 0.8. CONCLUSION PROM results in no significant changes in ICP or CPP in stable, neurosurgical patients in the absence of intracranial hypertension.

Bronchoscopic findings in post-obstructive pulmonary oedema

PurposeTo present the first photographed bronchoscopic findings associated with negative pressure pulmonary oedema (NPPE).Clinical featuresA previously healthy patient underwent anterior C3–C4 disc removal and arthrodesis. Following tracheal extubation he developed acute respiratory distress manifested as stridor, tachypnoea, restlessness, and desaturation. Once the trachea was reintubated, he displayed the classic findings of pulmonary oedema. Bronchoscopy was performed to confirm tracheal tube position and to rule out tracheal injury secondary to surgical manipulation. Diffuse punctate haemorrhages were noted throughout the visualised tracheobronchial tree.ConclusionWe believe that these haemorrhages represent disruption of the bronchial vasculature and may contribute to the clinical presentation of NPPE.RésuméObjectifPrésenter les premières photographies par bronchoscopie d’un oedème pulmonaire provoqué par une pression pulmonaire négative.Eléments clniquesUn patient jusque là bien portant subit une résection antérieure de disque à C3–C4 avec arthrodèse. Après l’extubation de la trachée, il développe une détresse respiratoire aiguë manifestée par du stridor, de la tachypnée, de l’agitation et de la désaturation. Une fois réintubé, il révèle les signes classiques d’un oedème pulmonaire. Une bronchoscopie est réalisée pour confirmer la position du tube endotrachéal et d’éliminer la possibilité de blessure trachéale secondaire à la manipulation chirurgicale. Des hémorragies diffuses ponctiformes sont notées sur l’arbre trachéobronchique.ConclusionNous croyons que ces hémorragies représentent la rupture de la vasculature bronchique et peuvent contribuer aux manifestations cliniques d’un oedème pulmonaire associé à une pression pulmonaire négative.

The effects of intentional hyperthermia on the Thrombelastograph and the Sonoclot analyser

The effect of whole-body hyperthermia (WBH) on viscoelastic properties of whole blood, as measured by the thrombelastogram (TEG) and Sonoclot analyser, was investigated in 10 patients undergoing WBH-carboplastin therapy for metastatic disease. Blood was taken from an existing central line at baseline (37 degrees C), during warming (39 and 41 degrees C) and cooling (39 and 37 degrees C). Sonoclot and TEG samples were analysed simultaneously at 37 degrees C and at the patients temperature with a temperature-compensated unit, except at 41 degrees C for the Sonoclot (maximum temperature adjustment of 40 degrees C). TEG measurements included R time (time to initial fibrin formation [mm]), K time (mm) and alpha angle (degrees) (both reflecting fibrinogen-platelet interaction), maximum amplitude (representing qualitative platelet function [mm]) and per cent fibrinolysis at 30 and 60 min. The Sonoclot ACT (SonACT-secs), initial rate of clot formation (%), time to peak amplitude (min) and peak amplitude of the Sonoclot signature (mm) were recorded. Decreased R time of the TEG compared to a marginally elevated baseline was found at all times during warming and cooling (p < 0.05). The K time was decreased at 41 degrees C compared to a normal baseline (p < 0.05). The SonACT was decreased (from an elevated baseline) at all other times, without differences in measures at patient temperature versus 37 degrees C (p < 0.05). The data suggest acceleration of fibrin formation during WBH to 41 degrees C in patients with malignancy. Implications for defining thromboembolic risk require further investigation.

Hypercalcitoninemia and Inappropriate Calciuria in the Acute Trauma Patient

PURPOSE This study was undertaken to determine the role of calcium-regulatory hormones (calcitonin [CT], parathyroid hormone [PTH], and vitamin D analogs) during the first 48 hours after acute trauma. METHODS Eleven acutely traumatized patients admitted to the shock-trauma intensive care unit (STICU) in a tertiary care teaching hospital were enrolled. Eleven same-day elective surgery patients served as the control group. Levels of ionized calcium (Ca2+), total calcium, magnesium, phosphate, CT, PTH, vitamin D analogs, electrolyte supplementation, and renal electrolyte loss were recorded during the first 48 hours after admission to the STICU. Control-group measurements consisted of Ca2+ and CT. RESULTS At admission, 91% of the patients had ionized hypocalcemia (1.04 +/- 0.10 mmol/L). Ca2+ levels increased significantly over time (1.13 +/- 0.08 at 24 hours; 1.16 +/- 0.07 at 48 hours) but remained below the control-group value (1.28 +/- 0.05; P < .05) despite supplementation. Ninety-one percent of the patients had increased CT values at admission, 91% at 24 hours, and 78% at 48 hours. Median CT values in the trauma patients were higher throughout the study than in the control group (P < .05). Urinary calcium loss in the trauma patients was within the normal range. PTH and vitamin D analog values were within the normal range throughout the study. Multiple regression analysis did not show any significant correlation between electrolytes and hormone or protein concentrations. CONCLUSIONS Acute trauma patients have ionized hypocalcemia associated with inappropriate urinary calcium loss, increased CT levels, and normal PTH and vitamin D analog values. We believe the degree of calciuria we observed was inappropriate in the context of ionized hypocalcemia. The cause of these increased CT levels is unclear. Our results suggest that Ca(2+)-regulatory mechanisms may be disrupted in the acute trauma patient.

Development criteria for academic leadership in anesthesiology: have they changed?

T he issues facing chairs of academic anesthesiology departments have changed quite dramatically over the past decade (1,2). The rapidly changing health care environment has placed academic anesthesiology departments at significant financial risk and dramatically impacted the recruitment of residents and faculty (1–3). Chairs of academic anesthesia departments have thus been faced with unprecedented challenges over the last decade that have forced increased dependence on clinical productivity from faculty (2,3). The impact of this increased pressure on the ability of academic physicians to pursue their primary missions of teaching, research, and academic career development is not well documented. We surveyed chairs of American academic anesthesiology departments and deans of American medical schools to evaluate the impact of the last decade on the selection criteria for academic chairs of anesthesiology. Traditional criteria, such as teaching experience and peer-reviewed research, as well as potential new criteria, such as formal business education, were evaluated. We also inquired about the availability of nonclinical time for potential chairs to pursue academic goals. The purpose of this study was to determine if the criteria for chairmanship of American academic anesthesiology departments have changed in light of the evolving health care environment.

Arterial blood sampling devices influence ionized calcium measurements.

OBJECTIVE To determine the effect of commercially available arterial blood sampling devices on ionized calcium measurements. DESIGN Prospective study. SETTING Neurosurgical and shock-trauma intensive care units (ICU) at a tertiary care teaching hospital. PATIENTS Fourteen patients admitted to the ICU. Each patient had an indwelling arterial catheter. INTERVENTIONS Arterial blood sampling. MEASUREMENTS AND MAIN RESULTS In 14 ICU patients, measurements of arterial blood ionized calcium concentrations were performed, using 12 different commercially available arterial blood sampling devices. Significant underestimation of ionized calcium in blood samples compared with the reference test tube (Vacutainer 45) was seen in seven of the devices. Arterial blood ionized calcium concentrations measured, using one commercially available syringe, were significantly higher compared with the reference test tube. There was no correlation between either the amount or type of heparin in the arterial blood sampling devices and arterial blood ionized calcium measurement. CONCLUSIONS This study demonstrates that various commercially available arterial blood sampling devices alter arterial blood ionized calcium measurements. These alterations are clinically important because ICU patients may be treated with inappropriate calcium supplementation.