Tacrine does not alter the potency of succinylcholine in the rat.

PURPOSE: Tacrine is a cholinesterase inhibitor used to manage Alzheimer's dementia. Given iv, it prolongs succinylcholine blockade in humans but the effects of chronic oral tacrine are not known. METHODS: Groups of adult rats were given 2.5 mg.kg-1 tacrine (chronic groups) or l ml saline (control) twice daily by gavage for one, two, four or eight weeks. An additional (acute) group received 2.5 mg.kg-1 tacrine iv. Twelve to 18 hr after the last gavage of tacrine or saline, and -20 min after iv tacrine, cumulative dose-response curves of succinylcholine were determined in the tibialis and soleus muscles in anaesthetized, ventilated rats during monitoring of evoked twitch response to indirect (nerve) train-of-four stimulation. RESULTS: The ED50 and ED95 of succinylcholine in control rats were (mean +/- SD) 204 +/- 41 and 382 +/- 96 micrograms.kg-1, respectively in the tibialis muscle, and 280 +/- 52 and 629 +/- 168 micrograms.kg-1 in the soleus muscle (P < 0.05 between muscles). In the acute and chronic tacrine groups, the mean ED50 and ED95 ranged from 166-197 and 277-396 micrograms.kg-1., respectively, in the tibialis muscle, and 248-333 and 546-667 micrograms.kg-1, in the soleus muscle. Dose responses did not differ among acute and chronic tacrine groups and the control group. CONCLUSION: Chronic oral tacrine does not alter muscle response to succinylcholine in the rat. This may not apply to Alzheimer patients receiving chronic tacrine since the interaction between acute tacrine and succinylcholine in the rat differs from that in humans.

The effects of chronic tacrine therapy on d-tubocurarine blockade in the soleus and tibialis muscles of the rat.

Tacrine (THA) is an anticholinesterase drug used to manage Alzheimer's dementia, but it is not clear how its chronic use might affect response to nondepolarizing muscle relaxants. We determined the magnitude and time course of the effects of chronic oral THA and of intravenous (IV) THA on d-tubocurarine (dTC) blockade at the soleus and tibialis muscles. Six groups of adult rats were given 10 mg/kg THA twice daily by gavage for 1, 2, 4, or 8 wk (chronic THA groups), or 1 mL of saline twice daily by gavage for 1-8 wk (control), or IV THA approximately 20 min before (acute), and the cumulative dose-response curves of dTC at the tibialis and soleus muscles were determined during indirect train-of-four stimulation in the anesthetized, mechanically ventilated rat. The 50% effective dose (ED50) and 95% effective dose (ED95) of dTC in control rats were (mean +/- SD) 30 +/- 10 and 61 +/- 18 microg/kg in the tibialis and 32 +/- 8 and 75 +/- 19 microg/kg in the soleus; respectively. IV THA increased the ED95 of dTC 2.5- to 3-fold (P < 0.05) but did not alter the ED50. Chronic THA increased both the ED50 and ED95 of dTC 1.5- to 2-fold (P > or = 0.05), and this effect tended to decrease with duration of THA therapy. We conclude that chronic THA therapy in rats causes resistance to dTC, with a tendency for the resistance to decrease with time, probably because of down-regulation of postsynaptic acetylcholine receptors. The same may apply to Alzheimer's patients taking THA chronically.

Heart rate changes in cardiac transplant patients and in the denervated cat heart after edrophonium.

PURPOSE: The effect of edrophonium on heart rate in cardiac transplant patients and in an animal model of acute cardiac denervation were studied, to evaluate the functional state of the peripheral parasympathetic pathway following cardiac denervation. METHODS: Edrophonium was studied in patients with normally innervated hearts (controls) and in cardiac transplants. Edrophonium was also studied in vagotomized, beta-blocked cats. In Group I animals, the vagus nerve was not stimulated. In Groups 2 & 3 the right vagus nerve was electrically stimulated to produce approximately 20% and 40% reductions in baseline heart rate, respectively. RESULTS: Maximum heart rate reduction in transplants (7.3 +/- 0.8 beats.min-1 with 0.6 +/- 0.08 mg.kg-1) was less than in controls (13.3 +/- 1.6 beats.min-1 with 0.4 + 0.05 mg.kg-1, P < 0.01). In Group I animals heart rate decreased maximally by 20.9 +/- 2.5 beats.min-1 with 9.0 +/- 1.9 mg.kg-1. In Groups 2 and 3, with doses < 1.5 mg.kg-1, reductions in heart rate were greater than in Group I and maximum reductions were obtained with lower doses (Group 2: maximum reduction by 20.3 +/- 2.8 beats.min-1 with 1.3 +/- 0.1 mg.kg-1; Group 3:22.6 +/- 4.0 beats.min-1 with 0.8 +/- 0.2 mg.kg-1, P < 0.001). Doses > 1.5 mg.kg-1 in Groups 2 and 3 produced increases in heart rate. CONCLUSION: Edrophonium produced bradycardia in cardiac transplants suggesting spontaneous release of acetylcholine from parasympathetic postganglionic neurons in the transplanted heart. The magnitude of the bradycardia was less in transplant than in control patients. Findings from animal studies suggest that the reduction in transplants can be attributed to diminution or absence of tonic cardiac parasympathetic drive. At high doses, edrophonium may interfere with parasympathetic neuron activation.

Neostigmine decreases heart rate in heart transplant patients.

PURPOSE: This study evaluated the effect of neostigmine on heart rate in cardiac transplant patients. METHODS: Neostigmine (2.5-50 micrograms.kg-1) was administered to ASA 1 or 2 patients with normally innervated hearts (controls), and to patients who had undergone recent (< six months before study) or remote (> six months before study) cardiac transplantation. RESULTS: Baseline heart rate was 66 +/- 3 beats.min-1 in controls (n = 10, mean +/- SEM), which was slower than that observed in recently (95 +/- 4 beats.min-1, n = 15, P < 0.001) and in remotely (88 +/- 3 beats.min-1, n = 16, P < 0.001) transplanted patients. Neostigmine produced a dose-dependent decrease in heart rate in all patients. Controls were the most sensitive to neostigmine, with a 10% decrease in heart rate produced by an estimated dose of 5.0 +/- 1.0 micrograms.kg-1. The recently transplanted group was the least sensitive, with the maximum dose producing only an 8.3 +/- 0.9% reduction. The response to neostigmine of the remotely transplanted patients was variable. The estimated dose to produce a 10% decrease in heart rate in this group was 24 +/- 6 micrograms.kg-1 which was greater than that for controls (P = 0.008). Administration of atropine (1.2 mg) reversed the neostigmine-induced bradycardia in all three groups. Reversal of the bradycardia consisted of a transient peak increase in heart rate in controls to 145 +/- 6% of baseline, a value which was greater than that observed in recent (103 +/- 1%, P < 0.001) and in remote (109 +/- 3%, P < 0.001) transplants. CONCLUSIONS: Neostigmine produces a dose-dependent bradycardia in heart transplant patients. Some remotely transplanted patients may be particularly sensitive to the bradycardic effects of neostigmine.

Neostigmine-induced bradycardia following recent vs remote cardiac transplantation in the same patient.

PURPOSE: This report describes the effects of neostigmine on heart rate in the same patient following recent and remote cardiac transplantation. CLINICAL FEATURES: Eighty-six months following the first transplant, neostigmine 5.0 micrograms.kg-1 i.v. produced a 10% reduction in heart rate which was reversed by atropine 1.2 mg. For 24 months prior to this initial study, the patient experienced angina, suggesting cardiac afferent reinnervation. Three months after the second heart transplant, a second study showed that a six-fold increase in the dose of neostigmine, 30.0 micrograms.kg-1, only produced a 3.5% reduction in heart rate which was reversed by atropine 1.2 mg. CONCLUSIONS: These observations indicate that neostigmine produces bradycardia following cardiac transplantation, and suggest that a greater response may be observed in remotely than in recently transplanted patients.

Diaphragmatic function before and after laparoscopic cholecystectomy.

BACKGROUND: Diaphragm dysfunction is a primary cause of ventilatory impairment after upper abdominal surgery. Laparoscopic procedures may result in less dysfunction. To test this, diaphragmatic function was studied in ten healthy adult patients undergoing elective laparoscopic cholecystectomy and in five undergoing laparoscopic hernia repair. METHODS: Respiratory gas exchange, ventilation, and breathing pattern were measured before and 3 h after surgery. Respiratory drive was evaluated from the relationship of P0.1 to end-tidal carbon dioxide (PETCO2) during tidal breathing. Diaphragm contractile function was assessed from maximal transdiaphragmatic pressure (Pdimax), and Pdi during a maximal sniff maneuver (Pdisniff). RESULTS: Oxygen consumption and carbon dioxide production did not change after surgery. Pdimax decreased by more than 50% in the laparoscopic cholecystectomy group, but Pdisniff did not change. Tidal volume and the ratio of inspiratory time over total cycle time decreased by 30% and 13%, respectively, PETCO2 increased by 9%, and minute ventilation did not change. In contrast, there was no variation in ventilatory function in patients undergoing laparoscopic hernia repair. In both groups, P0.1 did not change, which excludes depressed respiratory drive as an explanation for the decreased Pdimax in laparoscopic cholecystectomy. Contractile failure of the diaphragm was discounted as well, because Pdisniff did not change, even in the laparoscopic cholecystectomy group. CONCLUSIONS: Although laparoscopic cholecystectomy does not increase metabolic demands in the early postoperative period, it impairs diaphragm function. The internal site of surgical intervention appears to be the critical variable determining diaphragmatic inhibition after laparoscopic abdominal surgery.

Anaesthesia for a patient with central alveolar hypoventilation syndrome (Ondine's Curse).

The perioperative anaesthetic management of an adult patient with central alveolar hypoventilation syndrome (CAHS), Ondine's Curse, is described for anterior resection of a carcinoma of the bowel. This rare syndrome results in alveolar hypoventilation, hypercarbia, hypoxaemia with secondary polycythaemia, pulmonary artery hypertension, and cor pulmonale. Epidural morphine was used for postoperative analgesia in an attempt to improve postoperative respiratory function. However, postoperative mechanical ventilation was required until recovery of the respiratory drive, which was ablated by anaesthetic drugs, epidural morphine and high inspired oxygen concentrations. The pathophysiology and treatment of this syndrome are reviewed.

Anaesthesia for hip surgery in the elderly.

Surgical repair of hip fracture and total hip arthroplasty are primarily performed on elderly patients. Patients presenting for hip fracture surgery have a high prevalence of preoperative medical problems and may require medical stabilization before surgery. Regional anaesthesia for hip fracture repair may be contraindicated due to perioperative pharmacologic prophylaxis for deep venous thrombosis. The use of regional anaesthesia increases the magnitude and frequency of hypotensive episodes when compared with general anaesthesia. Intraoperative blood losses, averaging 250-300 ml, are not affected by anaesthetic technique. Following hip fracture surgery under spinal anaesthesia, patients exhibit better oxygenation in the early postoperative period than those after general anaesthesia. The frequency of postoperative confusion is unrelated to anaesthetic technique. The incidence of deep venous thrombosis is reduced following spinal anaesthesia as compared with general anaesthesia. The one-month mortality rate, approximately eight per cent, is unrelated to anaesthetic technique. Spinal, epidural and general anaesthesia have been used successfully for total hip arthroplasty. Intraoperative blood loss of 0.5-1.5 litres is reduced with regional anaesthesia. General anaesthesia with controlled hypotension also significantly reduces blood loss. Intraoperative instability with hypoxaemia, hypotension and cardiac arrest may follow impaction of the femoral prosthesis and are related to absorption of acrylic cement monomers and pulmonary embolism of fat, air, and platelet-fibrin aggregates. Postoperative deep venous thrombosis is common and the incidence may be reduced with epidural anaesthesia. Operative mortality is less than one per cent and pulmonary embolism is the commonest cause of death.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal pattern of breathing following cesarean section: epidural versus general anesthesia.

We tested the hypothesis that different anesthetic techniques for elective cesarean section would be reflected in the pattern of breathing and its control after birth. The pattern of breathing, including tidal volume, total breath duration (TTOT), minute ventilation, inspiratory (TI) and expiratory times, TI/TTOT ratio, and mouth occlusion pressure, was measured in 27 infants delivered by elective cesarean section during maternal epidural (lidocaine-carbon dioxide-epinephrine, n = 19) or general anesthesia (66% oxygen in N2O and 0.5% halothane, n = 8) at 10, 60, and 90 min and 3-5 days of age. Neonatal acid-base values and Apgar scores were within normal limits in both groups of infants. In general, at any given age the values of the respiratory parameters measured and their variability were similar between the two groups of infants. These findings indicate that the pattern of breathing after birth is not different following epidural or general anesthesia, and on the basis of our measurements, both epidural or general anesthesia appeared equally suitable for elective cesarean section.

Respiration in newborns: development of the control of breathing.

The pattern of breathing has been studied in human infants at 10, 60, and 90 min, and at a few days after birth. The major characteristics of the pattern of breathing in the immediate period after birth is a marked variability that decreases progressively with time. Interruptions of expiration and peak expiratory flows occurring late in expiration are common findings at 10 to 90 min of age but are infrequent at a few days. From 10 to 90 min to a few days of life the tidal volume increases and respiratory rate decreases with no changes in minute ventilation. The decrease in respiratory rate is due to proportional increases in both inspiratory and expiratory time. Infants born vaginally behave similarly to those delivered by cesarean section except with regard to tidal volume, which at 10 min is closer to the value measured at a few days; this may be the result of the mechanics of the vaginal delivery, which results in less fluid to be absorbed from the lung at birth. Vagal respiratory reflexes are present at birth and the prolongation of inspiratory time during occlusion at end expiration appears to decrease from 10, 60, and 90 min to a few days of age. Values of mouth pressure at 0.1 s after an occlusion at end expiration are higher at 10 min after birth than at 60 and 90 min. Because mean inspiratory flow is similar in this time period it could indicate a progressive increase in the compliance of the respiratory system, possibly reflecting the absorption of pulmonary fluid.

Onset of respiration in infants delivered by cesarean section.

We studied the ventilatory parameters and the pattern of breathing including the onset of respiration in 20 healthy infants immediately after cesarean-section delivery. In eight of the infants further measurements were obtained at 60 min of life. The pattern of breathing immediately after delivery is very irregular with a marked tendency to keep the lung inflated mainly through interruptions of expiration. After the first expiration some air remains in the lung representing the formation of functional residual capacity (FRC). FRC obtained with the first breath is proportional to the previous inspired volume and is the largest contribution towards the full establishment of FRC. Tidal volume and FRC of the first breath are similar to that reported in babies delivered vaginally, which suggests that the forces required for lung inflation are similar in the two groups of infants. The first breath tends to be deeper and slower and has a longer expiratory time than subsequent breaths. At 60 min of life the respiratory pattern becomes more regular, tidal volume is further decreased, and respiratory frequency is increased through a reduction of expiratory time.

Meperidine infusion for postoperative analgesia in grossly obese patients.

Postoperative analgesia was provided to nine grossly obese patients with a continuous intravenous meperidine infusion. The narcotic was infused at an initial rate of 1.3 mg . min-1 for 45 minutes, then 0.7 mg . min-1 for 30 minutes followed by 0.5 mg . min-1 for the next 24 hours. Pain was assessed at hourly intervals, serial blood samples were taken for measurement of plasma meperidine concentrations, and respiratory function was assessed by serial measurement of vital capacity and arterial blood gas analysis. Analgesia was gradual in onset and from six hours after commencement of the infusion, seven of the patients suffered little or no pain. Plasma meperidine concentrations reached a peak of 0.33 +/- 0.05 microgram . ml-1 at one hour decreased gradually after three hours. Surprisingly, there was poor correlation between analgesia and plasma meperidine concentration. All patients breathed spontaneously and maintained satisfactory blood gas tensions. However, there was a marked reduction in postoperative vital capacity. Thus meperidine administered by continuous intravenous infusion can provide good postoperative analgesia in the obese patient without producing respiratory depression. However, the lack of correlation between analgesia and plasma narcotic concentration suggests that further study is required before intravenous regimes can be prescribed by application of pharmacokinetic principles.

Anaesthesia for the morbidly obese. Experience with 110 patients.

The anaesthetic management and postoperative complications of 110 grossly obese patients undergoing weight-reducing surgery have been reviewed. The major problems were technical, related to the bulk of the patient, and respiratory, caused by alterations in pulmonary physiology. Extradural catheters were placed in 70 patients before induction of general anaesthesia. In all patients the trachea was intubated during anaesthesia and the lungs ventilated with large tidal volumes and appropriate inspired oxygen concentrations. Muscle relaxation was achieved with extradural block in 35 patients; the remainder received pancuronium i.v. Extradural analgesia with bupivacaine provided excellent analgesia after surgery and greatly facilitated nursing care.

Plasma cortisol concentrations during Caesarean section.

The effects of extradural and general anaesthesia on the adrenocortical response to elective or emergency Caesarean section were studied in 72 patients. Maternal plasma concentrations of cortisol were measured before surgery, at delivery, and 30 and 60 min after skin incision. Umbilical vein and artery plasma cortisol concentrations at delivery were determined also. Maternal plasma cortisol concentrations in patients receiving extradural anaesthesia did not change significantly from control at any of the time intervals. In the general anaesthesia group concentrations were significantly increased from control, at 30 and 60 min after skin incision for elective Caesarean sections, and at 60 min after skin incision during emergency surgery. There were no significant differences between the mean umbilical vein and artery plasma cortisol concentrations compared within or between extradural or general anaesthesia groups. Extradural anaesthesia, in contrast to general anaesthesia, decreases the adrenocortical response to Caesarean section surgery by blocking afferent neurogenic pathways from the surgical site. The method of anaesthesia does not influence the fetal cortisol response.

Oxygen consumption during spontaneous ventilation with continuous positive airway pressure: assessment in normal volunteers and patients with acute respiratory failure.

Continuous positive airway pressures (CPAP) of 0.49 kPa and 0.98 kPa were applied to ten healthy volunteers and nine critically ill patients with acute respiratory failure. A modified Godart-Statham NV 16003 spirometer was used to measure respiratory frequency (f), tidal volume (VT), oxygen consumption (VO2), and changes in functional residual capacity (delta FRC). During CPAP of 0.49 kPa, volunteers had a decrease in f, and increased VT and minute volume (MV). At 0.98 kPa CPAP, f did not change but VT and MV significantly increased. VO2 did not change at either pressure. The volume of delta FRC increased with an increased level of CPAP. The entire volunteer group was comfortable throughout the whole study. When CPAP was applied to acutely ill patients, f decreased. VT and MV increased at both CPAP pressures. delta FRC was similar to the volunteers. VO2 in the patient group rose significantly at 0.49 and 0.98 kPa CPAP. Some of the patients were uncomfortable with 0.49 kPa pressure, while all the patients were distressed at 0.98 kPa CPAP. The effects of increased oxygen consumption and patients discomfort should be considered in critically ill patients receiving CPAP therapy.