Jack Chalon

Obesity as an Independent Risk Factor for Cardiovascular Disease: A 26-Year Follow-up of Participants in the Framingham Heart Study

The relationship between the degree of obesity and the incidence of cardiovascular disease (CVD) was reexamined in the 5209 men and women of the original Framingham cohort. Recent observations of disease occurrence over 26 years indicate that obesity, measured by Metropolitan Relative Weight, was a significant independent predictor of CVD, particularly among women. Multiple logistic regression analyses showed that Metropolitan Relative Weight, or percentage of desirable weight, on initial examination predicted 26-year incidence of coronary disease (both angina and coronary disease other than angina), coronary death and congestive heart failure in men independent of age, cholesterol, systolic blood pressure, cigarettes, left ventricular hypertrophy and glucose intolerance. Relative weight in women was also positively and independently associated with coronary disease, stroke, congestive failure, and coronary and CVD death. These data further show that weight gain after the young adult years conveyed an increased risk of CVD in both sexes that could not be attributed either to the initial weight or the levels of the risk factors that may have resulted from weight gain. Intervention in obesity, in addition to the well established risk factors, appears to be an advisable goal in the primary prevention of CVD.

The Antagonistic Effect of Pentazocine on Fentanyl Induced Respiratory Depression Compared with Nalorphine and Naloxone

The effect of pentazocine, a strong analgesic with a weak opiate antagonistic activity, on fentanyl-induced respiratory depression was studied after anaesthesia in patients undergoing gynaecological laparotomy. Pentazocine (1 mg/kg) was given intravenously at the end of operation. The postoperative respiratory depression in these patients was compared with that in patients who received strong opiate antagonists, nalorphine and naloxone, or no opiate antagonists. Respiratory depression was evaluated by measuring respiratory rate, respiratory minute volume and blood gases. The results show that pentazocine has a clear antagonistic effect on fentanyl-induced respiratory depression but the effect of 1 mg/kg is weaker and shorter than that produced by 5 mg of nalorphine or 0.4 mg of naloxone. Postoperative analgesia in patients who received pentazocine was not longer than that in patients who received no opiate antagonists at the end of the operation.

Pharmacokinetics and Pharmacodynamics of 4-Aminopyridine in Anesthetized Dogs

The pharmacokinetics and pharmacodynamics of 4-aminopyridine (4-AP), a drug which antagonizes nondepolarizing neuromuscular blockade, were studied in seven anesthetized dogs. Using a constant infusion of pancuronium, force of the anterior tibialis contraction in response to stimulation of the sciatic nerve was depressed to 10% of the control tension (90% depression of twitch tension). After 20 min of steady state, 4-AP (1.0 mg/kg) was administered i.v. Serum, urine and bile samples were analyzed for 4-AP concentration at several intervals for 10 hr after administration of 4-AP, using a sensitive high-performance liquid chromatographic assay (1 ng/ml). Serum data best fit a three-compartment pharmacokinetic model. The volume of the central compartment was 412 +/- 352 ml/kg (mean +/- S.D.) and the volume of distribution at steady state was 2517 +/- 363 ml/kg. Initial half-lives were 1.1 +/- 0.7 and 25.4 +/- 11 min. The terminal elimination half-life was 125 +/- 23 min and total clearance was 21 +/- 4 ml/kg/min. Of the injected dose, 60 +/- 9% was recovered in the urine and only 0.01 +/- 0.01% of the dose was recovered in the bile in 10 hr. Inasmuch as renal clearance of 4-AP exceeded glomerular filtration rate we conclude that 4-AP undergoes tubular secretion into the urine. The pharmacodynamic results included an onset time of 14 +/- 8 min, peak effect (maximum percentage of antagonism of twitch tension depression) 97 +/- 27% and duration of action 219 +/- 54 min. We conclude that 4-AP has a longer serum elimination half-life and a longer and more variable duration of action than other antagonists (i.e., neostigmine and pyridostigmine) of nondepolarizing neuromuscular blockade.

Cerebral Protection by Isoflurane During Hypoxemia or Ischemia

The cerebral metabolic effects of isoflurane suggest that it may provide a degree of cerebral protection similar to that demonstrated for barbiturates. Accordingly, the possible cerebral protection afforded by isoflurane against hypoxemia and ischemia was studied in mice and dogs, respectively. In mice breathing 5% oxygen survival time was increased significantly over control in groups exposed to 1.0% and 1.4% isoflurane. At higher concentrations (2.0% and 3.0%) it is presumed that cardiorespiratory depression contributed to shorter survival times. In six dogs the effects of 3% isoflurane on the rates of cerebral ATP and phosphocreatine depletion and lactate accumulation during incomplete global ischemia were compared with six control dogs exposed to N2O. Incomplete global ischemia was produced by acute hemorrhagic hypotension to 30 mmHg for 9 minutes, a situation that does not abolish cortical electrical activity (active EEG). In the dogs exposed to isoflurane, the cerebral energy stores of ATP and PCr and the cerebral energy charge were sustained at significantly higher levels than in dogs exposed to N2O, and the cerebral lactate accumulation was significantly less in the initial 7 minutes of hypotension. It is concluded that in the circumstances of oxygen deprivation insufficient to abolish cortical electrical activity, isoflurane, like the barbiturates, can provide some cerebral protection presumably by depressing cortical electrical activity and cerebral metabolism.

Results of Hepatic and Hemopoietic Controls in Hospital Personnel Exposed to Waste Anesthetic Gases

The authors report on pollution measures in some operating theatres and consider biological data for the hepatic and hemopoietic functions in operating room personnel and in control groups. Waste gas concentrations range from 17.3 to 22.6 ppm for enfluorane and from 500 to 1275 for N2O in theatres not equipped with antipollution systems. Pollution is 3-8 times lower when a scavenging system is present, while with horizontal laminar air flow exhaust in function, the gas concentration in the air is insignificant. Tests for the hepatic and hematological functions, done on 61 operating room personnel, 87 ward nurses, and 69 technicians and physicians of radiology services, do not show any significant difference between those exposed to anesthetic gases and controls.

Lidocaine Given Intravenously as a Suppressant of Cough and Laryngospasm in Connection with Extubation After Tonsillectomy

The preventive effect of lidocaine against coughing in the recovery period after general anaesthesia was observed. The study was carried out as a double-blind sequential trial. At the same time the incidence of laryngospasm was registered. Lidocaine or placebo was given intravenously just before extubation. Nineteen patients for tonsillectomy, all of them over the age of 15, randomly received a 2% solution of lidocaine 2 mg/kg body weight or placebo (saline) 2 min prior to expected extubation. We found that lidocaine in this dose given prophylactically just before extubation was able to inhibit and prevent coughing in the recovery period after general anaesthesia. None of the patients included in this study got laryngospasm, and none of the patients developed serious side-effects.

Plasma Lignocaine Concentrations Following Topical Laryngeal Application

Lignocaine 4%, 4 mg/kg, was sprayed onto the larynx and subglottic area of 96 children aged from 2 weeks to 12 years and plasma lignocaine concentrations were measured. While the majority were well within the accepted safe range (4.5 micrograms/ml) occasional concentrations over 8 micrograms/ml appeared in all groups. Simultaneous arterial and venous sampling showed a small but significant difference in the first 10 minutes.

Limitations of Jet Ventilation Through the Laryngoscope

A series is presented of 100 patients who underwent direct laryngoscopy under general anaesthesia. Our preferred technique of ventilation is jet insufflation by an injector attached to the blade of the laryngoscope, as it provides the surgeon with a quiet and completely exposed larynx. In nine cases, chest expansion was assessed as inadequate by the anaesthetist. These patients were obese with a short neck, and/or stiff-necked; thus, insertion of the laryngoscope was difficult and a good seal between it and the larynx could not be achieved. Arterial blood gas values in six of these patients demonstrated marked hypoventilation. To improve ventilation in these patients an alternative technique of insufflation through a nasotracheal catheter was used. Arterial blood gas values indicated that this method resolved the problem of hypoventilation. Although the catheter somewhat limits the view of the endolarynx, the improved ventilation outweighs the drawbacks of this technique. It is suggested that for the obese and/or stiff-necked patient, a nasotracheal catheter be used electively for ventilation.

Protamine Sulphate Hypersensitivity

Protamine hypersensitivity has been documented by intra-dermal skin testing in three patients who demonstrated sudden cardiovascular collapse and bronchospasm following the use of intravenous protamine sulphate. All patients had been given protamine previously. The effects of the anaphylactic response were terminated quickly by the administration of intravenous adrenaline associated with plasma volume expansion. Intra-dermal skin testing against all anaesthetic agents is recommended so that the specific allergen can be identified. In patients who are shown to be allergic to protamine sulphate and who require cardiac or vascular surgery careful monitoring of heparin dosage and neutralisation with hexadimethrine (Polybrene) intravenously appears to be a safe alternative.

Repeated Doses of Suxamethonium

Repeated sub-apnoeic doses of suxamethonium produce increased neuromuscular block in a hand muscle, measured by integrated electromyogram. The response to the initial dose varies widely between patients. More than 50% of patients showed evidence of non-depolarising block after one dose of suxamethonium. There was a variation between the response of the hand muscle and respiratory muscles.