A patient's condition may alter the pharmacokinetic and pharmacodynamic characteristics of local anaesthetics and so increase the risk of toxicity. In the elderly patient, the elimination half-life is increased for both lidocaine and bupivacaine; the risk of overdose is therefore increased when the local anaesthetic agent is given in repeated doses and as a continuous infusion. Cardiotoxicity due to bupivacaine seems to be worsened by pregnancy. In the foetus and newborn, local anaesthetic toxicity gives the same clinical picture as in the adult and is increased in the presence of acidosis and anoxia. Bupivacaine depressive effects are increased by tachycardias, intraventricular blocks and all the conditions which are known to depolarize the cardiac cell membrane (e.g. hyperkaliemia, acidosis, severe hypoxia, myocardial ischaemia). Drug interactions may also potentiate the toxicity of lidocaine and bupivacaine, such as calcium blockers and diazepam. The effects of other conditions (cirrhosis, renal failure, epilepsy) and other drug interactions, specially those modifying free fraction and elimination of local anaesthetics, are also discussed.

Age Factors↗

PubMed1988

Pharmacokinetics of midazolam in anaesthetized cirrhotic patients.

The pharmacokinetics of midazolam were compared in cirrhotic patients (n = 10) and control patients (n = 9), during general anaesthesia. Total plasma clearance was 637 +/- 223 ml min-1 (mean +/- SD) in control patients and 402 +/- 170 ml min-1 in cirrhotic patients (P less than 0.05). The total volume of distribution was similar. Elimination half-life was 135 +/- 40 min in controls and 168 +/- 30 min in cirrhosis (P less than 0.05). Protein binding was evaluated by equilibrium dialysis in both groups at two concentrations of midazolam: 20 and 500 micrograms litre-1. No saturation occurred, but the free fraction was 4.9 +/- 1.7% in cirrhotic patients, compared with 1.9 +/- 0.6% in controls (P less than 0.01). Despite its mainly hepatic elimination, midazolam disposition appears to be only slightly impaired in cirrhotic patients.

Adult↗

PubMed1988

[Atypical muscular syndrome with myolysis during long-term treatment with fibrates].

Acute inflammatory muscular syndromes secondary to clofibrate therapy are rare. They usually present with muscular pain in all four limbs with biochemical signs of rhabdomyolysis. The outcome is favourable as a rule with rapid regression of the clinical and biochemical changes after stopping the responsible drug. The authors report an atypical case of this syndrome with chest pains suggestive of angina.

Clofibrate↗

PubMed1988

Ventilatory effects of continuous epidural infusion of fentanyl.

The effects of a continuous epidural administration of fentanyl on pain and on ventilation were studied in eight patients scheduled for orthopedic surgery of the knee. In each subject, epidural fentanyl was given by a bolus dose of 1 microgram.kg-1, followed by a continuous infusion of 1 microgram.kg-1.h-1 over 18 hours. Ventilatory measurements were performed during quiet breathing and during CO2 stimulation tests before surgery. After surgery measurements were made before epidural administration of fentanyl; 1, 2, 5, 18 hours after the start of epidural fentanyl infusion; and 6 hours after its discontinuation. Adequate pain relief was achieved in all patients during fentanyl administration. No significant change in ventilation was noted during quiet breathing. The slope of the ventilatory response to CO2 (VE/PaCO2) decreased significantly from 1.46 +/- 0.2 to 0.75 +/- 0.1 L.min-1.mm Hg-1 (mean +/- SEM; P less than 0.05) one hour after the onset of fentanyl administration, and remained stable throughout the infusion. Eighteen hours after the onset of epidural fentanyl infusion, VE/PaCO2 was still 0.76 +/- 0.14 L.min-1.mm Hg-1. At the end of fentanyl administration, plasma fentanyl levels measured in six patients had progressively increased from 0.42 +/- 0.02 ng.ml one hour after the onset of the infusion to 1.54 +/- 0.19 ng.ml at the end of the infusion. These results suggest that a continuous epidural administration of fentanyl is a technique of analgesia that can provide adequate pain relief but which is associated with ventilatory depression. However, with the doses used in this study, the ventilatory depression remained moderate and of no demonstrable clinical consequence.

Adult↗

PubMed1987

[Refractory cancer pain. Subarachnoid or epidural administration of morphine].

Spinal analgesia, a new method for relieving refractory cancer pain, was tested in 19 patients. A catheter was installed in the subarachnoid (17 cases) or peridural (2 cases) space and connected to a subcutaneous site of injection. The success rate at 10 days was 68%. In 11 patients pain was relieved throughout the course of the malignant disease, with doses that did not exceed 6 mg in 7 patients and 10 mg in the remaining 4 patients. The most severe complications were leakage of the cerebrospinal fluid in 1 case, meningitis after 18 months of injection in 1 case and displacement of the catheter in 3 cases.

Adult↗

PubMed1987

Continuous i.v. infusion of labetalol for postoperative hypertension. Haemodynamic effects and plasma kinetics.

Labetalol is a combined alpha- and beta-adrenoreceptor blocking agent. A loading dose may be used to antagonize sympathetic overactivity rapidly after surgery and be followed by a continuous infusion to achieve a stable effect. The haemodynamic effects and pharmacokinetics of this method of labetalol administration were studied in six rewarmed, extubated and sedated patients 15 +/- 2 h after aortobifemoral bypass surgery. Patients were monitored with radial and thermistor-tipped pulmonary artery catheters. Labetalol 1.5 mg kg-1 was injected i.v. over 5 min and a maintenance infusion of 0.2 mg kg-1 h-1 was started 30 min later and continued for 5.5 h. Within 5 min of the loading dose, i.v. labetalol induced significant (P less than 0.05) decreases in mean arterial pressure (-32 +/- 11%), in heart rate (-20 +/- 11%) and in cardiac index (-26 +/- 15%) that lasted throughout the infusion. Changes in systemic vascular resistance were not uniform, but an increase was not observed in any patient. Mean stroke volume index and ventricular filling pressures were not significantly affected by labetalol administration. The mean measured steady state plasma concentration (Css) (264 +/- 46 ng ml-1) was higher than predicted (170 ng ml-1) because the clearance (13.1 +/- 2.4 ml kg-1 min-1) was lower than that used to calculate the infusion rate. We conclude that labetalol is an effective antihypertensive agent in the postoperative period. A Css can be achieved rapidly by such i.v. administration and this offers the advantage of inducing rapid and stable haemodynamic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Morphine pharmacokinetics in renal failure.

The effect of chronic renal failure (RF) on the pharmacokinetics of morphine was studied in nine patients with end-stage RF, aged 58 +/- 8 yr (SD), and in seven control patients, aged 58 +/- 15 yr, undergoing peripheral surgery under general anesthesia. All patients received 0.2 mg X kg-1 as an intravenous bolus injection. Blood samples were collected over a 36 h period, and plasma concentrations were measured using a specific radioimmunoassay method. Unchanged morphine could be identified for only 12 h in all patients. The mean plasma concentrations of unchanged morphine were similar in the two groups, except in the first sample (5 min) where it was higher (P less than 0.05) in RF group. Patients with RF had a significantly smaller (P less than 0.05) central compartment (0.3 +/- 0.2 l X kg-1 versus 0.8 +/- 0.4 l X kg-1) than in the controls. Volume of distribution at steady state was also significantly (P less than 0.05) decreased in RF patients (2.8 +/- 1.0 l X kg-1) versus 3.7 +/- 1.2 l X kg-1 in the normal patients. The total apparent volume of distribution, the elimination half-life, and the plasma clearance were similar in the two groups. Identical peak levels of morphine metabolites were observed in the two groups, but plasma concentration of morphine metabolites was undetectable after 12 h in the control group and remained at a high level of 82 +/- 49 ng X ml-1 at 24 h and 83 +/- 57 ng X ml-1 at 36 h in RF patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

PubMed1987

Effect of an intubating dose of succinylcholine and atracurium on the diaphragm and the adductor pollicis muscle in humans.

This study compares the neuromuscular blocking effect of succinylcholine (0.8 mg . kg-1) and atracurium (0.6 mg.kg-1) on the diaphragm (D) and the adductor pollicis (AP) in 20 patients anesthetized with nitrous oxide, oxygen, and fentanyl. The diaphragm was monitored by measuring transdiaphragmatic pressure following bilateral phrenic nerve stimulation. After succinylcholine, the time from injection of succinylcholine to maximum depression of the single twitch response (onset time) was of 50 +/- 11 s (+/- SD) for D compared to 80 +/- 24 s for AP (P less than 0.001). After succinylcholine, recovery from paralysis was earlier for D than AP. Single twitch height (TH) returned to 25% of its control value (T25) after 5 +/- 2 min for D compared to 7 +/- 3 min for AP (P less than 0.001). Complete recovery of TH (T100) was achieved after 9 +/- 4 min for D and 11 +/- 5 min for AP (P less than 0.01). Recovery index (T25-75) was of 2 +/- 1 min for both muscles. After atracurium, the onset time for D was of 137 +/- 31 s compared to 181 +/- 45 s for AP (P less than 0.001). The T25 was achieved after 38 +/- 7 min for D compared to 63 +/- 13 min for AP (P less than 0.001). The TH of D returned to T100 after 60 +/- 12 min compared to 87 +/- 17 min for AP (P less than 0.01). The train-of-four ratio returned to 1 after 64 +/- 15 min for D compared to 99 +/- 21 min for AP (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

The neuromuscular blocking effect of vecuronium on the human diaphragm.

This study compares the neuromuscular blocking effect of vecuronium (0.1 mg/kg) on the diaphragm and the adductor pollicis in nine anesthetized patients. Monitoring of the diaphragm consisted of measurement of the transdiaphragmatic pressure after bilateral phrenic nerve stimulation. Onset time for neuromuscular blockade of the diaphragm was 1.6 +/- 0.3 min (+/-SD) compared to 2.5 +/- 0.3 min in the adductor pollicis (P less than 0.001). The diaphragm recovered earlier and more rapidly than the adductor pollicis. The twitch height (TH) returned to 25% of its control value after 27 +/- 8 min for the diaphragm, compared to 41 +/- 11 min for the adductor pollicis (P less than 0.01). Complete TH recovery was achieved after 49 +/- 14 min for the diaphragm and after 74 +/- 22 min for the adductor pollicis (P less than 0.01). The recovery index of 12 +/- 4 min for the diaphragm was significantly shorter (P less than 0.05) than for the adductor pollicis (20 +/- 9 min.) We conclude that monitoring of peripheral muscles in anesthetized patients given vecuronium provides adequate information about the degree of paralysis of the diaphragm.

Adult↗

PubMed1987

[Myocardiopathies of Friedreich's disease].

Cardiac involvement in Friedreich's disease is classically a hypertrophic myocardiopathy, concentric or assymmetrical with or without dilatation. It has nothing specific in comparison to other myocardiopathies. Nevertheless, forms with a dilated myocardiopathy are also possible, but much more unfrequent. A propos of three cases, we have studied the different aspects of myocardiopathies in Friedreich's ataxia. The problem raised by the case of an hypertrophic myocardiopathy evolving toward a dilated form, unusual element of this pathology, is presented. The therapeutic potential of hypertrophic myocardiopathies is classically represented either by beta-blockers or by the more recent slow calcium inhibitors.

Adult↗

PubMed1987

Pharmacokinetics of alfentanil in chronic renal failure.

The pharmacokinetics of alfentanil were studied during general anesthesia in nine patients with renal failure and in ten patients with normal renal function. All patients received 0.05 mg/kg alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 8 hr, using a specific radioimmunoassay technique. Protein binding was measured by equilibrium dialysis. Elimination half-life and plasma clearance were similar in both groups. The volume of distribution at steady state was greater (P less than 0.02) in patients with renal failure (405 +/- 86 ml/kg) than in patients with normal renal function (281 +/- 97 ml/kg). Patients with renal failure had a higher (P less than 0.01) alfentanil plasma free fraction (0.19 +/- 0.06) than patients with normal renal function (0.11 +/- 0.03). When kinetic parameters were corrected for protein binding, the unbound volume of distribution and the free drug clearance were unchanged in patients with renal failure. These results suggest that the modification of alfentanil free fraction in renal failure does not induce any change in elimination but may influence the distribution of alfentanil.

Adult↗