Plasma renin activity and forearm blood flow in paraplegic humans.

We recently found that paraplegic humans respond to hyperthermia with subnormal increase in skin blood flow (SkBF), based on measurements of forearm blood flow (FBF). Is this inhibition of SkBF a defect in thermoregulation or a cardiovascular adjustment necessary for blood pressure control? Since high resting plasma renin activity (PRA) is found in unstressed individuals with spinal cord lesions and since PRA increases during hyperthermia in normal humans, we inquired whether the renin-angiotensin system is responsible for the attenuated FBF in hyperthermic resting paraplegics. Five subjects, 28-47 yr, with spinal transections (T1-T10), were heated in water-perfused suits. Blood samples for PRA determinations were collected during a control period and after internal temperature reached approximately 38 degrees C. Some subjects with markedly attenuated FBF had little or no elevation of PRA; those with the best-developed FBF response exhibited the highest PRA. Clearly, circulating angiotensin is not the agent that attenuates SkBF. Rather, increased activity of the renin-angiotensin system may be a favorable adaptation that counters the locally mediated SkBF increase in the lower body and thus allows controlled active vasodilation in the part of the body subject to centrally integrated sympathetic effector outflow.

Sweat rate vs. forearm blood flow during lower body negative pressure.

Skin blood flow is inhibited when hyperthermia and added hypovolemic stresses are superimposed. We tested the hypothesis that part of this inhibition is a reduced drive for cutaneous active vasodilatation (AVD) with sweat rate (SR) taken as an indirect measure of the efferent drive for cutaneous AVD. We also inquired whether SR itself changes with redistribution of blood volume. Six healthy supine men were subjected to lower body negative pressure (LBNP) after heating in water-perfused suits increased esophageal temperatures (Tes) to a mean of 37.2 degrees C and at least doubled SR and forearm vascular conductance (FVC). Heating continued throughout LBNP and recovery. Sweat rate did not decrease with LBNP onset, although SR-Tes slopes during LBNP were reduced 28% from control. In four subjects the SR-Tes slope did not recover when LBNP was discontinued. These observations suggest that SR is not an effector of the low-pressure baroreflex. In contrast to SR, FVC abruptly fell 22% at the onset of LBNP. Thereafter, FVC-Tes slopes near zero or less occurred. The major effector for FVC inhibition with LBNP appears to be the neural vasoconstrictor system. A minor component due to reduced drive for cutaneous AVD probably occurs as well.

Unaltered norepinephrine-heart rate relationship in exercise with exogenous heat.

We measured plasma norepinephrine (NE) concentration, an index of sympathetic nervous activity, and epinephrine (E), an index of adrenal medulla activity, in six normal young men during mild to severe exercise, with and without superimposed heat stress. The primary objective was to observe whether the normally close relationship between heart rate and log NE concentration in upset when heart rate at a given work load is increased by heat stress. Exercise, beginning at 50 W, was graded in 50-W increments lasting 10 min each up to 200 W, which lasted 5-10 min. Each subject went through the protocol twice, once with skin temperature kept low by a water-perfused suit and then with skin temperature raised to 38 degrees C. Exogenous heart stress raised log circulating NE concentration in proportion to the rise in heart rate at a given work load so that the usual relationship between these variables, previously observed during other stresses, was preserved. In contrast to some other stresses, heat stress had no added effect on E concentration, indicating that this stress during exercise raises sympathetic neural activity (as reflected in the rise in NE) without stimulating additional adrenal release of E.

Cystic fibrosis, vasoactive intestinal polypeptide, and active cutaneous vasodilation.

The transmitter substance for the active cutaneous vasodilation that accompanies sweating during hyperthermia in humans is unknown. Hökfelt et al. (Nature Lond. 284: 515-521, 180) hypothesized that it is vasoactive intestinal polypeptide (VIP) that is cotransmitted with acetylcholine. Heinz-Erian et al. (Science Wash. DC 229: 1407-1408, 1985) reported that VIP innervation is sparse in the skin of persons with cystic fibrosis (CF). A corresponding attenuation of active vasodilation in these subjects would be evidence that VIP is involved in this effector mechanism of human thermor-regulation. Immunocytochemical analysis of skin biopsies from four men with CF confirmed that VIP innervation was sparse. We also analyzed immunoreactivity for calcitonin gene-related peptide (CGRP; normal), substance P (normal), and neuropeptide Y (low). VIP-immunoreactive Merkel cells were abnormal. Despite sparse VIP-immunoreactive innervation, our CF subjects' cutaneous vascular responses to hyperthermia were normal. Because VIP was not completely absent, this evidence is insufficient to rule out VIP as the vasodilator transmitter. However, the CGRP and substance P innervation we observed could mean that release of one or both of these peptides was the mechanism of the fully developed active cutaneous vasodilation.

Does acute hypoxemia blunt sympathetic activity in hyperthermia?

Sympathetic alpha-adrenergic function is depressed by hypoxemia per se; does addition of another sympathoexcitatory stimulus elicit normal responses in other sympathetic effector pathways? We activated by hyperthermia four sympathetic pathways: alpha-adrenergic [norepinephrine (NE) release], beta-adrenergic [plasma renin activity (PRA)], cholinergic (sweating), and peptidergic (active vasodilation). In the first test, five normothermic men were exposed to hypoxemia for 10 min (control), then hypoxemia plus heat for 30 min, and then heat with normoxia for 8-10 min over a continuous 48- to 50-min period. Heating was controlled with a water-perfused suit. Time courses and magnitudes of heat-induced increments in body temperature, forearm blood flow, and sweat rate were normal during hypoxemia and unaffected by switching to normoxia. Hypoxemia exaggerated increases in plasma NE, epinephrine, PRA, and heart rate but had no additional effects on blood pressure. In a second 50-min test (2 men) with normoxic control (10 min), heating plus normoxia (20 min), and heating plus hypoxemia (20 min), effects of hypoxemia on all variables were as in the first test. Thus, acute moderate hypoxemia did not blunt active cutaneous vasodilation or sweating and exaggerated increases in catecholamines and heart rate, indicating maintained peripheral autonomic function.

Transesophageal Doppler scanning versus thermodilution during general anesthesia. An initial comparison of cardiac output techniques.

Measurement of cardiac output has become an essential feature of anesthetic management of patients with cardiac disease requiring operation. Thermodilution by way of a Swan-Ganz catheter is the current popular technique for cardiac output determination. Unfortunately, this method is costly and has an associated irreducible morbidity rate and has, in rare instances, resulted in death. The suprasternal ultrasonographic Doppler technique has shown promise for measuring cardiac output noninvasively; however, it is too cumbersome for continuous intraoperative use. In an effort to overcome this limitation, the esophageal stethoscope was modified to accept a Doppler probe. Herein, we have reported an initial comparison of transesophageal Doppler scanning and thermodilution in 23 adult men during general anesthesia. The average difference between thermodilution and descending cardiac output was 0.16 +/- 0.81 liters/min. The correlation between thermodilution and descending cardiac output increased with operator experience. In the last 13 patients, there was an average correlation of 0.85. After the equipment was mastered and improvements in design were made, descending cardiac output had a high correlation with thermodilution and appeared to track the dynamic changes during general anesthesia.

EEG suppression and increased blood-brain barrier permeability following intracarotid injection of iothalamate meglumine (Conray) in dogs.

Over a 2-year period we observed three cases of unilateral suppression of the electroencephalogram (EEG) lasting from 45 s to 4 min following intracarotid injection of 60% iothalamate meglumine (Conray) for intraoperative carotid angiography postendarterectomy. As a result of these cases we undertook studies in 11 dogs anesthetized with isoflurane to examine causes of EEG suppression following intracarotid contrast medium injection. In group 1 (n = 6) cerebral blood flow (CBF), the cerebral metabolic rate for oxygen (CMRO2), EEG activity, and permeability of the blood-brain barrier (BBB) were determined. In group 2 (n = 5) cerebrospinal fluid (CSF) pressure, EEG activity, and BBB permeability were determined. Intracarotid injection of 5 ml of 60% Conray was associated with unilateral EEG suppression and increased BBB permeability in 1 of 11 dogs. Injection of contrast material caused no change in CBF or CMRO2 and caused a statistically significant but physiologically unimportant increase of CSF pressure (from 12 +/- 1 to 16 +/- 1 cm H2O, mean +/- SEM). It is concluded that EEG suppression following intracarotid injection of Conray is a rare event. It seems unlikely that EEG suppression resulted from cerebral ischemia or hypoxia, but rather was associated with increased BBB permeability. Increased BBB permeability likely was caused by the osmotic effect of Conray and not by hypoxic-ischemic microvascular injury or loss of autoregulation of CBF.

Calcium channel blockers do not enhance increases in plasma potassium after succinylcholine in humans.

STUDY OBJECTIVE: To determine whether chronic calcium channel blocker therapy exaggerates the rise in plasma potassium concentration ([K+]) after succinylcholine administration. DESIGN: Prospective clinical study. SETTING: University and Veterans Affairs hospitals. PATIENTS: 36 ASA physical status III and IV male patients: 21 patients taking chronic calcium channel blockers and 15 patients not receiving calcium channel blockers, all of whom were scheduled for inpatient surgical procedures with general anesthesia. INTERVENTIONS: In all patients, anesthesia was induced with high-dose opioids plus a sedative-hypnotic, and intubation was facilitated with 1 to 1.5 mg/kg succinylcholine without nondepolarizing neuromuscular blocker pretreatment. MEASUREMENTS AND MAIN RESULTS: Plasma [K+] was measured prior to induction and 1, 3, 5, 8, 11, and 15 minutes after succinylcholine was administered. A modest average peak rise of 0.5 mEq/L in plasma [K+] was observed, but there were no differences between patients who were or were not receiving calcium channel blockers. CONCLUSIONS: Patients receiving chronic calcium channel blocker therapy are at no greater risk of hyperkalemia after succinylcholine than those not taking such medications.

Trends in quality of anesthesia care associated with changing staffing patterns, productivity, and concurrency of case supervision in a teaching hospital.

BACKGROUND: The authors used continuous quality improvement (CQI) program data to investigate trends in quality of anesthesia care associated with changing staffing patterns in a university hospital. METHODS: The monthly proportion of cases performed by solo attending anesthesiologists versus attending-resident teams or attending-certified registered nurse anesthetist (CRNA) teams was used to measure staffing patterns. Anesthesia team productivity was measured as mean monthly surgical anesthesia hours billed per attending anesthesiologist per clinical day. Supervisory ratios (concurrency) were measured as mean monthly number of cases supervised concurrently by attending anesthesiologists. Quality of anesthesia care was measured as monthly rates of critical incidents, patient injury, escalation of care, operational inefficiencies, and human errors per 10,000 cases. Trends in quality at increasing productivity and concurrency levels from 1992 to 1997 were analyzed by the one-sided Jonckheere-Terpstra test. RESULTS: Productivity was positively correlated with concurrency (r = 0.838; P<0.001). Productivity levels ranged from 10 to 17 h per anesthesiologist per clinical day. Concurrency ranged from 1.6 to 2.2 cases per attending anesthesiologist. At higher productivity and concurrency levels, solo anesthesiologists conducted a smaller percentage of cases, and the proportion of cases with CRNA team members increased. The patient injury rate decreased with increased productivity levels (P = 0.002), whereas the critical incident rate increased (P = 0.001). Changes in operational inefficiency, escalation of care, and human error rates were not statistically significant (P = 0.072, 0.345, 0.320, respectively). CONCLUSIONS: Most aspects of quality of anesthesia care were apparently not effected by changing anesthesia team composition or increased productivity and concurrency. Only team performance was measured; the role of individuals (attending anesthesiologist, resident, or CRNA) in quality of care was not directly measured. Further research is needed to explain lower patient injury rates and increases in critical incident reporting at higher concurrency and productivity levels.

Placement of esophageal stethoscope by acoustic criteria does not consistently yield an optimal location for the monitoring of core temperature.

The esophageal stethoscope has evolved into a device for both acoustic and core temperature monitoring. To test whether routine placement according to acoustic criteria results in placement of the core temperature sensor in the region of contiguity between the esophagus and the heart, we determined the depth of placement electrocardiographically. All patients were undergoing nonthoracic elective operations requiring general anesthesia and tracheal intubation. First, we established that different observers selected the same esophageal depth within +/- 1 cm electrocardiographically, using the criterion of a symmetric biphasic P wave of maximal amplitude (7 patients). Then, in 30 more patients, we compared routine acoustic placements with the depths of the maximal-amplitude biphasic P wave. Stethoscopes placed according to acoustic criteria were within +/- 3 cm of P-wave depths in 15 of 30 patients. In the remaining patients, measured discrepancies ranged up to 13.5 cm. We conclude that the prevailing stethoscope design, with a thermistor at the tip, below the acoustic window, does not ensure placement of the thermistor within the optimal region for monitoring of core temperature. A modification in design that would take advantage of the reliability of electrocardiographic positioning is suggested.

Cardiovascular responses to muscle ischemia in man--dependency on muscle mass.

We sought to determine whether the pressor response to exercise-induced muscle ischemia is related to the mass of tissue rendered ischemic. Six men repeatedly exercised for 5 min at a fixed load between 75 and 150 W (bicycle ergometer). Thirty seconds before the end of exercise, circulation to one calf, two calves, one leg, and two legs was arrested with pneumatic cuffs in successive tests with 15-min recovery periods interspersed. Each occlusion was maintained until the 3rd min of exercise recovery. During postexercise occlusion we observed 1) mean arterial pressure (MAP) was elevated in proportion to the mass of ischemic muscle, 2) forearm blood flow (FBF) was elevated during the overlap of occlusion with exercise but did not show a uniform response during the following 3 min of occlusion--either vasoconstriction or vasodilation occurred, 3) heart rate (HR) was elevated only when two legs were occluded, and 4) occlusion did not affect ventilation or endtidal CO2. We conclude that the ischemic pressor response is muscle mass-dependent. Our findings suggest that the baroreflex alters peripheral vascular resistance so as to aid in the maintenance of elevated MAP.

Cutaneous vascular response to exercise and acute hypoxia.

Six normal young men were studied during 50 min of moderate exercise (100-137 W) that included one 15-min (protocol 1) or two 10-min periods of breathing 11-12% O2 (in N2) (protocol 2). Absolute work intensity was kept constant for each subject, but relative severity increased during hypoxia owing to reduction in maximum O2 uptake. Our question was whether hypoxia causes cutaneous vasoconstriction; this in turn should cause a rise in esophageal temperature (Tes) and a shift in the forearm skin blood flow (SkBF)-Tes relationship. In all subjects forearm blood flow (FBF) (venous occlusion plethysmography) rose throughout exercise and Tes tended to stabilize. Neither 10- nor 15-min periods of hypoxia caused systematic changes in FBF or Tes or their relationship to each other. We conclude that hypoxia equivalent to that incurred at 4,500-5,000 m does not significantly alter the short-term regulation of SkBF and body temperature during moderate exercise. Net cutaneous vasoconstriction is not elicited by arterial chemoreflexes under these conditions.

Hemodynamic response and change in organ blood volume during spinal anesthesia in elderly men with cardiac disease.

Aging and disease may make the elderly patient with cardiac disease particularly susceptible to hypotension during spinal anesthesia. We studied 15 men, 59-80 y old, with histories of prior myocardial infarction (n = 9), congestive heart failure (n = 2), and/or stable myocardial ischemia (n = 11) given spinal anesthesia with 50 mg lidocaine in dextrose. Technetium-99m-labeled red blood cell imaging estimated left ventricular ejection fraction (EF) and changes in blood volume in the abdominal organs and legs. Arterial and pulmonary artery catheters provided hemodynamic measurements. Sensory block averaged T4 (range T1-10). Mean arterial pressure decreased 33% +/- 15% (SD) (P < 0.001), secondary to decreases in vascular resistance (SVR), -26% +/- 13% (P < 0.001) and cardiac output, -10% +/- 16% (P = 0.03). EF increased from 53% +/- 11% to 58% +/- 14% (P < 0.001) while left ventricular end-diastolic volume (LVEDV) decreased (-19% +/- 9%, P < 0.001). Blood volume increased in the legs (6% +/- 6%, P = 0.006), kidneys (10% +/- 9%, P < 0.001), and mesentery (7% +/- 5%, P 0.001) but not in the liver or spleen. Cardiac function was well maintained. We concluded that the primary mechanism of hypotension was a decrease in SVR, not cardiac output, despite the decrease in LVEDV.

Effect of spontaneous sighs on arterial oxygenation during isoflurane anesthesia in humans.

The presence, frequency, and volume of spontaneous sighs was evaluated in 21 (ASA 1-2) supine patients aged 44 +/- 15.2 (SD) yr, during isoflurane-nitrous oxide anesthesia. Before induction the inspiratory capacity of each patient was determined. After induction of anesthesia and tracheal intubation patients breathed spontaneously except for three manual inflations to each patient's predetermined inspiratory capacity at the beginning and end of surgery. Arterial blood gas tensions were measured before and 5 min after each set of mechanical deep breaths and each hour during surgery, the mean duration of which was 2 +/- 0.09 hr. Spontaneous sighs occurred in 13 of 21 patients. The average frequency was 6 +/- 4 sighs/hr. At FIO2 = 0.5, nonsighing patients had an initial PaO2 of 229 +/- 59 mm Hg and sighers had an initial PaO2 of 162 +/- 57 mm Hg (P less than 0.05). Arterial oxygen did not change in sighing patients during the course of surgery, while in nonsighing patients the PaO2 decreased from the initial value of 229 +/- 60 mm Hg to 170 +/- 63 mm Hg (P less than 0.05). Mechanical deep breaths administered at the end of surgery produced no improvement in oxygenation in either sighers or nonsighers. The presence or absence of sighs did not correlate with PaO2 or PACO2. Though the results suggest that spontaneous sighs in some patients may function to help maintain arterial oxygenation, all patients maintained their PaO2 while breathing spontaneously under general anesthesia in the supine position.

Propranolol reduces bupivacaine clearance.

Propranolol reduces the clearance of lidocaine by both reducing hepatic blood flow and inhibiting lidocaine metabolism. The authors investigated the possibility that propranolol reduces the clearance of bupivacaine as well. Bupivacaine, 30-50 mg, was administered intravenously to six normal human volunteers, over 10-15 min on two occasions, at least 2 weeks apart. Propranolol, 40 mg orally every 6 h, was used on one occasion, beginning 24 h prior to the bupivacaine administration. The sequence of the sessions was randomized. Twenty-two venous blood samples were obtained over 36 h in order to determine bupivacaine clearance, terminal elimination rate constant, and volume of distribution. All subjects experienced mild CNS toxicity, consisting of tinnitus, facial tingling, or subtle visual disturbances, associated with peak venous plasma concentrations of 0.81 to 2.7 micrograms/ml. Mean bupivacaine clearance was 0.33 +/- 0.12 l/min for the control session and 0.21 +/- 0.12 l/min during propranolol use, a significant 35% reduction (P less than 0.01). The terminal elimination rate constant (beta) was 0.27 +/- 0.16 h-1 for the control session and 0.14 +/- 0.069 h-1 with propranolol (P less than 0.05); terminal elimination half-lives were 2.6 and 4.9 h, respectively. Volume of distribution was unchanged. Because bupivacaine clearance should be relatively insensitive to hepatic perfusion, it appeared that propranolol caused a substantial inhibition of bupivacaine metabolism at the level of the hepatocyte. These data suggest that concomitant use of propranolol could result in the accumulation of a toxic concentration of bupivacaine.

Respiratory effects of nalbuphine and butorphanol in anesthetized patients.

A double-blind, randomized study was conducted in 16 patients who were anesthetized with 50% nitrous oxide in oxygen and given either 0.17 mg/kg butorphanol or 0.86 mg/kg nalbuphine, and whose respiratory depression was assessed by the response of minute ventilation to increasing carbon dioxide concentrations. The slopes of the carbon dioxide ventilatory response curves [delta VE/delta PCO2(L.min-1 X %CO2(-1)] were 7.45 +/- 1.17 with nalbuphine and 2.42 +/- 0.56 with butorphanol. Butorphanol caused significantly (P less than 0.025) greater respiratory depression than nalbuphine. The results of this study caution against the indiscriminate use of butorphanol in the perianesthetic setting.

Microcomputer-based data acquisition system for clinical research.

We have described a computerized data acquisition system for clinical investigation that can record over fifty physiologic variables from up to twenty-four electronic monitors. The information is acquired by a personal computer using RS-232C serial communications and analog-to-digital conversion. In its present configuration the system records information from a Spacelabs 500 series physiologic monitor, Hewlett-Packard physiologic monitor with the Careport computer interface, SARA mass spectrometer, Nellcor pulse oximeter, Neurotrac processed EEG, Lawrence cardiac output monitor, Hewlett-Packard capnometer, and Bourns spirometer. The software can be easily modified to accommodate other physiologic monitors. The system records parameter or waveform information and writes the data into a file that can be accessed by commercially available graphical and statistical packages. The data acquisition system is easy to use, transportable, and inexpensive.

Vasomotor control in healed grafted skin in humans.

Do the vasomotor functions unique to skin recover in a skin graft? To determine whether locally mediated vasodilation and active reflex vasodilation recovery, we applied direct heating and whole-body heating, respectively. Also, presence of sympathetic cutaneous vasoconstriction was tested with application of lower body negative pressure (LBNP) during local heating. Subjects were six men who had been severely burned. Forearm blood flow (FBF) was recorded (venous occlusion plethysmography) in regions with healed split-thickness circumferential grafts. All subjects responded normally to local heating of the forearm (irrigation with 42 degrees C water). All but one showed cutaneous vasoconstriction in response to LBNP. Three subjects responded normally to whole-body heating with water-perfused suits (oral temperature elevation approximately 1.5 degrees C); two subjects had attenuated responses. No active vasodilation was normal cutaneous vasomotor functions return in (or under) split-thickness skin grafts, recovery and associated thermoregulatory function may be attenuated or absent, perhaps in relation to the survival of dermis.

Splanchnic vasoconstriction in heat-stressed men: role of renin-angiotensin system.

We conducted a two-part study to determine whether the renin-angiotensin system contributes to the rise in splanchnic vascular resistance (SVR) during heat stress (rectal temperature was raised 1 degree C). In experiment 1 (control) seven men on a normal salt diet were directly heated (water-perfused suits) for 40-50 min. Arterial pressure (85 Torr) was unchanged; plasma renin activity (PRA) rose from 102 to 239 ng angiotensin I.100 ml-1.3 h-1; and SVR increased 73% (from 63 to 109 units). Experiment 2 was a repetition of experiment 1 on the same subjects, except that propranolol (10 mg iv) was given at the onset of heating to block renin release. Propranolol attenuated the rise in heart rate and reduced mean arterial pressure from 82 to 72 Torr; it blocked the rise in PRA with heating in two subjects, reduced it in three, but increased it in two. Although changes in SVR paralleled those in PRA in three subjects, SVR still rose 60% (from 58 to 99 units) after PRA rise was blocked. In both experiments, plasma norepinephrine concentration rose indicating increased sympathetic nervous activity. During mild heat stress, increased PRA is not a major factor in the increase of SVR.