Louis R. Orkin

Computer Analysis of Postanesthetic Deaths

Of 34,145 consecutive surgical patients who were attended by an anesthesiologist, 645 died within the first seven days. Two prime determinants of mortality emerged: 1) the physical status of the patient, and 2) the judgment and skill of the physicians. Mortality was highest in cardiovascular and brain surgery, in patients of advanced age, and in emergency surgery. However, this was principally a reflection of the higher incidences of poor-risk patients in these groups. Mortality was highest with local anesthesia, lowest with regional analgesia, and intermediate with general anesthesia. Again, this was mainly an expression of the numbers of poor-risk patients anesthetized with the particular methods. Four per cent of the deaths (1:1,265 cases) were related to anesthetic management and 3 per cent (1:1,707 cases) to postoperative management. Deaths attributable to anesthesia occurred as late as the sixth postoperative day, and two-thirds were judged preventable.

Placental Transmission of Nitrous Oxide

Placental transmission of nitrous oxide Was studied in 14 patients during elective cesarean section and in 26 patients during vaginal delivery. Duration of ancsthesia varied between 2, and 19 minutes. Randomly-selected patients were hyperor hyporcntilated. Umbilical vein nitrous oxide levels ranged from 55 to 91 per cent of maternal values (average 79 per cent). The fetal-maternal nitrous oxide concentration ratio showed no correlation with incidence of uterine contractions, duration of anesthesia (after the first two minutes), or materanal pH (7.32–7.59) or Paco2 (14–41 torr). Umbilical artery nitrous oxide levels ranged from 31 to 90 per cent of the umbilical vein levels. The umbilical artery-vein nitrous oxide concentration ratio increased progessivcly with increasing durations of anesthesia. The data demonstrate rapid transmission of nitrous oxide across the human placenta as well as rapid uptake by the fetus.

Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 10. Beta-adrenoceptor blockade and coronary artery surgery

Abstract In an attempt to resolve the controversy concerning propranolol therapy in patients undergoing coronary artery revascularization surgery, 54 consecutive patients with stable angina pectoris receiving chronic propranolol therapy entered a randomized trial and were compared with 17 patients on no propranolol therapy (group I). The 54 patients were divided into three treatment groups: in group II (n = 17) propranolol was abruptly withdrawn 48 hours prior to surgery, in group III (n = 18) propranolol was abruptly withdrawn 10 hours prior to surgery, in group IV (n = 19) propranolol was maintained until the day of surgery, half the usual dose was given 2 hours prior to surgery, and intravenous propranolol was administered every four hours postoperatively. Patients in group II and III had significantly higher increases in the rate-pressure product (RPP) during intubation, and in the postoperative periods compared to patients in groups I and IV. Group IV had the lowest increase in RPP during intubation and a significantly lower incidence of postoperative supraventricular arrhythmias. Patients abruptly withdrawn from propranolol, at 10 or 48 hours preoperatively, are more prone to increments in myocardial oxygen demands than those patients not treated with propranolol postoperatively or who were maintained on the drug. Plasma renin activity, although lower in patients treated with propranolol (group IV), did not seem to play a role in the RPP increments seen. The increased sympathetic tone associated with intubation and the postoperative period most likely contribute to the increments in RPP and the increased incidence of arrhythmia. These data show that (1) propranolol may be given safely to patients at the time of coronary artery bypass and may be maintained postoperatively without a decrement in left ventricular performance; (2) there is a “rebound effect” or increased sympathetic activity in patients who have propranolol abruptly withdrawn 10 or 48 hours prior to surgery. This “rebound effect” causes a marked increase in myocardial oxygen demands during intubation and the postoperative periods, with an increased incidence of arrhythmias. (3) Continuous propranolol treatment up until the time of surgery with maintenance of intravenous therapy in the immediate postoperative period provides protection against these complications. (4) The data and implications can reasonably be expected to apply to propranolol-treated patients with angina pectoris undergoing general anesthesia and noncardiac surgical procedures.

Localization and Measurement of Microvascular and Microcirculatory Responses to Venous Pressure Elevation in the Rat

The effect of increase in regional draining venous pressure on the response of mesoappendix microvasculature and microcirculation was studied by direct microscopic methods in vivo .

Tetanic Fade and Post-Tetanic Tension in the Absence of Neuromuscular Blocking Agents in Anesthetized Man

Frequency and time dependent changes in neuromuscular transmission were examined in 30 patients undergoing elective minor surgical procedures not requiring the use of muscle relaxants. Anesthesia was induced with sodium thiopenthal and maintained with N2O-O2 and fractional doses of mepcridine or fentanyl.Neuromuscular function was measured by recording the force of thumb adduction evoked by supramaximal stimulation of the ulnar nerve at the wrist. Single stimuli were applied every 2.5 seconds as square pulses of 0.1-millisecond duration. Tetanic trains of 10-second duration ranging from 10 Hz to 400 Hz were used.From analysis of present data, criteria for normal responses to 10-second tetanic trains of varying frequencies were established. At a frequency of 30 Hz, the tetanic response is fully maintained and followed by post-tetanic potentiation; at a frequency of 50 Hz, both tetanic and post-tetanic responses are maintained; at a frequency of 100 Hz, there is tetanic fade, followed by a post-tetanic depression of the single indirect twitch responses.It is concluded that frequency and duration of indirect stimulation are the most important factors in using tetanic maintenance and post-tetanic events in assessment of recovery from neuromuscular block.

A Method for Determining Minimum Alveolar Concentration of Anesthetic in the Rat

Minimum alveclir concentrations (MAC) for halothane and methoxyflurane were determined at two stimulus intensities in the rat. Forty-three rats were anesthetized with halothane or methoxyflurane in oxygen, and after tracheostomy were ventilated with a Harvard Rodent Respirator. Anesthetic agents were delivered by a nonrebreathing circuit, with the animals body temperature maintained at 37 ± 0.1 C. End-tidal gas was obtained by intermittently stopping the respirator at end-expiration and withdrawing 0.2–0.3 ml of gas from the tracheostomy. When three successive end-tidal samples taken over 15 minutes had the same anesthetic concentration, the rats tail was clamped with either a bulldog artery clamp or a hemostat and the response noted. MAC was determined as the mean of the lowest alveolar concentration preventing and the highest permitting movement in response to the two stimuli. For halothane, MACs were 0.82–0.12 per cent when the bulldog clamp was used in eight rats and 1.17 ± 0.51 per cent with the hemostat in 15 rats. MACs for methoxyflurane were 0.22 ± 0.05 per cent with the bulldog clamp in eight rats and 0.27 ± 0.03 per cent with the hemostat in 12 rats.

Cerebrospinal fluid pressures during halothane anaesthesia.

SummaryChanges in cerebrospinal fluid pressure, venous pressure, and arterial pressure induced by different concentrations of halothane were measured in ten elderly patients prior to the beginning of surgery. Cerebrospinal fluid and venous pressures were recorded by a water manometer and arterial pressure with a sphygmomanometer. Tidal volume, pH, and pCO2 were determined intermittently in order to prevent changes in respiratory physiology. The patients were intubated with a cuffed endotracheal tube and given 1/2 to 2 vol. per cent halothane, for periods of 15 minutes or longer, using a non-rebreathing system and a Fluotec vaporizer.Two types of increase in cerebrospinal fluid pressure were noted. During endotracheal intubation, cerebrospinal fluid pressure rose sharply while venous pressure lagged behind and arterial pressure changed in a variable manner. During the period of undisturbed halothane anaesthesia, elevations of cerebrospinal fluid pressure corresponded with increases in the venous pressure, while arterial pressure decreased concomitantly. The magnitude of these changes was proportional to the concentration of halothane.The implications of these findings on the administration of halothane anaesthesia during neurosurgical operations are discussed.RésuméChez dix malades âgés, nous avons mesuré avant le début de la chirurgie les changements de la pression du liquide céphalorachidien, dp sang veineux et du sang artériel, qui surviennent au cours de l’ induction de l2019;anesthésie au fluothane à diverses concentrations. Les pressions du liquide céphalorachidien et du sang veineux ont été prises au moyen d’ un manomètre à l’ eau et la pression du sang artériel au moyen d’ un sphygmomanomètre. Pour éviter des changements daas la physiologie respiratoire, nous avons calculé, de façon intermittente, l’ air courant, le pH et 1e pCO2. Tous les malades étaient incubés avec un tube à ballonnet et, durant 15 minutes ou plus, recevaient du fluothane à des concentrations variant de 1/2 à 2 vol. per cent, en employant la vaporisateur fluotec et un système sans réinspiration.Nous avons observé deux sortes d’ augmentation de pression du liquide céphalo-rachidien. Au cours de l’ intubation endotrachéale, la pression du liquide céphalorachidien s’ est élevée en flèche, la pression du sang veineux est demeurée basse et la pression du sang artériel a présenté des variantes. Au cours de la période de distribution de l’ agent anesthésique, les augmentations de la pression du liquide céphalorachidien correspondaient aux augmentations de la pression du sang veineux, pendant que la pression du sang artériel diminuait au même moment.

Effects of Anesthetics on the Response ofthe Microcirculation to Circulating Humors

REPORTS pertaining to the effects of humoral factors on the reaction of the microcirculation during anesthesia are few and not without unanswered questions. On the one hand, our knowledge of the mechanisms participating in the regulation of the microcirculation is incom-plete, and on the other, “humors” or chemical messengers carried by the blood stream to dis-tant target organs and tissues are not the only chemical factors which may affect the vascular smooth muscle receptors of the capillary bed. Data are being accumulated which indicate that the so-called “local hormones” 1, 2 or “tissue mediators” 3 are of considerable importance in modifying microcirculatory dynamics. Dif-ficulties arise from the rather scanty systematic studies on the interplay of these vasoactive humors with various anesthetic agents. Within the scope of this symposium, we should like to describe certain aspects outlined as follows: (1) a brief description of current concepts of the microcirculation to bring into better per-spective the main subject of this discussion, (2) present information on the modification of microcirculatory homeostatic mechanisms by anesthetic agents, and, (3) the possible re-lationship of the microcirculatory reaction under anesthesia to circulating humors in the hope that this may stimulate further thought and study.

CORTISOL AND ANTIDIURETIC HORMONE RESPONSES TO STRESS IN CARDIAC SURGICAL PATIENTS

The hormonal responses to anaesthesia and cardiac surgery were studied in patients undergoing valve or coronary bypass surgery. Marked increases in antidiuretic hormone levels as a result of surgical stress were seen, and were of approximately equal magnitude in both groups. Although both groups also showed marked increases in plasma cortisol levels in response to operations, this response appeared to be relatively blunted in valve surgery patients, especially at the end of operation and in the intensive care unit. This blunted cortisol response may be a manifestation of exhaustion of adrenocortical reserves in valvular surgical patients whose sympathoadrenal system has already been chronically stimulated by a low output state.The important role of the neuroendocrine system in maintaining homeostasis postoperatively has long been recognized; this relative cortisol deficiency may be aetiologically related to poor postoperative recovery in critically ill valvular surgery patients.RéSUMéLes réponses hormonales à l’anesthésie et à la chirurgie ont fait l’objet de la présente étude effectuée chez un groupe de malades soumis à une chirirgie valvulaire ainsi que chez ceux d’un second groupe subissant une chirurgie coronarienne. On a observé une élévation marquée de 1’hormone anti-diurétique secondaire au stress de la chirurgie et cette élévation était semblable chez les patients des deux groupes. Le taux du cortisol s’est également élévé chez les patients des deux groupes en réponse au stress chirurgical, mais cette réponse était atténuée chez les valvulaires, en particulier en fin d’intervention et dans la phase postoperatoire immédiate. Une telle réponse chez les valvulaires peut refiéter l’epuisement des réserves adreno-corticales chez des patients dont le système adreno-sympathique a été stimulé de façon chronique par la présence d’un bas débit cardiaque.Le rôle important du systéme neuro-endocrinien dans le maintien du l’homoéostase post-opératoire est connu depuis longtemps; la déficience relative en cortisol peut contribuer ç une évolution post-opératoire difficile chez des patients en condition critique.

Microvascular Hypersensitivity Subsequent to Chemical Denervation

Microscopic observation and micrometric measurements of microarterial vessels in the mesentery of the anesthetized rat, during chemical interference with the vasomotor nerve supply, showed (A) marked (average 25×) hypersensitization to epinephrine; (B) persistent vasoconstriction; and (C) depression or cessation of vasomotion. These and concomitant similar reactions of the precapillary sphincter resulted in relative ischemia and frequent reversal of blood flow through the endothelial capillary network. A comparable hypersensitization to epinephrine, observed in six isolated perfused microarterial vessels, upon shift in internal static pressure strongly suggests that the change in reactivity of the vascular smooth muscle cell seen in vivo might also be related to a local change in transmural pressure. The plot of the logarithm of epinephrine threshold concentration vs. the approximate circumferential wall tension (computed for selected in vivo and in vitro experiments neglecting wall thickness) showed a steep rise in vessel sensitivity occurring concomitantly with decrease in wall tension. Thus it appears that hypersensitization of microarterial muscle cells which develops during the hypotensive episode of acute chemical nerve blockade in the rat may be primarily related to a modification in wall tension.