Effect of short-term smoking halt on carboxyhemoglobin levels and P50 values

Fifteen informed volunteers who smoked one to two packs of cigarettes per day were studied to measure changes in carboxyhemoglobin levels and P50 after smoking was stopped for 12 hr. Before smoking was stopped, carboxyhemoglobin levels (6.55 +/- 0.40%) were above normal, and the P50 (22.92 +/- 0.25 mm Hg) was significantly shifted to the left. After smoking was stopped for 12 hr there was a significant decrease in carboxyhemoglobin levels to 1.06 +/- 0.16% (P less than 0.001), and P50 shifted towards normal to 26.41 +/- 0.14 mm Hg (P less than 0.001). The authors conclude that within even as little as 12 hr after cessation of smoking, carboxyhemoglobin and P50 levels change towards normal values.     

Histamine2 receptor blocker in the treatment of protamine related anaphylactoid reactions: two case reports

Two case reports are described of acute anaphylactoid reactions following the administration of protamine to reverse the anticoagulation effect of heparin in patients undergoing coronary artery bypass graft surgery. The administration of cimetidine seemed to reverse the anaphylactoid reaction after conventional treatment with epinephrine, H1 receptor blocker, and steroids had failed. We recommend that H2 receptor blockade be included with other drugs in the treatment of anaphylactoid reactions following protamine, and possibly after anaphylactoid reactions associated with other substances.     

In vitro effects of fluoride and bromide on pseudocholinesterase and acetylcholinesterase activities

The in vitro effects of two metabolites of inhalational anaesthetics, fluoride and bromide, on pseudocholinesterase (PCHE) and acetylcholinesterase (ACHE) activities in the blood samples of seven healthy patients were studied. The PCHE and ACHE activities were determined by kinetic spectrophotometric methods. Fluoride at the levels achieved with clinical concentrations of enflurane and sevoflurane (25-75 microM.L-1) inhibited PCHE activity by 28-65 per cent (P less than 0.01) and ACHE activity by less than five per cent (P greater than 0.05). Bromide at the levels achieved with clinical concentrations of inhalational anaesthetics had no significant effect on either PCHE or ACHE activity. We recommend caution when succinylcholine and/or ester type local anaesthetics are used in the immediate postoperative period following enflurane or sevoflurane anaesthesia. We also recommend that blood drawing for PCHE activity be delayed at least until 24 hr following enflurane or sevoflurane anaesthesia.     

The effects of neurokinin A,neurokinin B,and eledoisin on substance P analysis

Commercial sources for neuropeptide radioimmunoassays have made this sensitive tool available to clinical investigators for monitoring the potential involvement of neuropeptides in pain modulation. We measured substance P-like immunoreactivity in the plasma, saliva, and pericardial fluid of subjects with and without pain (chronic and acute) to determine if substance P levels are altered. Some recent studies have suggested that substance P in various body fluids may be a correlate of chronic pain. To test this correlation it is important to ensure that the assay is measuring what it was designed to measure. Therefore, the influence of three tachykinins on the analysis of substance P concentrations was assessed with a commercially available radioimmunoassay kit. A small (approximately 2 to 6%), apparently nonspecific elevation in measured substance P was found when alpha-neurokinin, beta-neurokinin, or eledoisin was incubated with substance P and its antibody. Our results also indicate an apparent specific affinity of the substance P antibody for alpha-neurokinin (above 1,000 pg/ml) and beta-neurokinin (above 5,000 pg/ml). Substance P levels in the body fluids we tested ranged from 0.47 to 62.88 pg/mg protein (47.4 to 230.8 pg/ml). Levels of the tested tachykinins have not been determined in body fluids. If alpha-neurokinin or beta-neurokinin is found to be present in high concentrations in these fluids, this commercially available substance P kit may overestimate substance P levels. The concentrations of tachykinins necessary to interfere specifically with the assay are 10- to 100-fold higher than substance P in body fluids. If the other tachykinins are present at concentrations similar to the substance P levels, we would not expect them to interfere substantially with the accuracy of our measurements of substance P using this assay. This study was funded in part by the Study Center for Anesthesiology Toxicology, Vanderbilt University Medical Center, Nashville, TN. We thank Incstar Corporation, Stillwater, MN, for providing the substance P radioimmunoassay kits.     

Effect of magnesium on plasma cholinesterase activity

Plasma cholinesterase activity levels were studied in 15 pregnant patients with preeclampsia before and after the administration of therapeutic doses of magnesium sulfate. Plasma cholinesterase activity was also studied in 15 healthy nonpregnant and 15 healthy pregnant women. The mean plasma cholinesterase activity level in pregnant patients with preeclampsia before and after the administration of magnesium sulfate was 179 +/- 26 and 176 +/- 39 units/ml, respectively. The healthy nonpregnant patients and healthy pregnant patients had a plasma cholinesterase activity level of 426 +/- 85 and 264 +/- 24 units/ml, respectively. Our data demonstrated that magnesium has no significant effect on plasma cholinesterase activity. Our data also confirm that there is a significant reduction in plasma cholinesterase activity in pregnant patients with preeclampsia compared with either healthy nonpregnant or healthy pregnant patients. We conclude that the low level of plasma cholinesterase activity is probably responsible for the prolonged action of succinylcholine in pregnant patients with preeclampsia receiving magnesium sulfate.     

Propranolol pretreatment reduces cardiorespiratory toxicity due to plain,but not epinephrine-containing,intravenous bupivacaine in rats

The purpose of this study was to evaluate the effects of pretreatment with propranolol on the cardio-respiratory toxicity of bupivacaine, either plain or with epinephrine 1:200,000 (5 μg · ml^{? 1}) added. Adult male Sprague Dawley rats, anaesthetized with intraperitoneal pentobarbital, were divided into four groups. Groups I and III were pretreated with iv propranolol 150 μg · kg^{? 1}, and Groups II and IV recei ved iv NS as a placebo. Three minutes later, rats in Groups I and II received plain 0.5% bupivacaine, 4 mg · kg^{? 1}, and Groups III and IV received 4 mg· kg^{? 1} of 0.5% bupivacaine with epinephrine, 5 μg · ml^{? 1} iv. Five of eight rats pretreated with propranolol survived (Group I), compared with uniform fatality with NS pretreatment (Group II) (P < 0.05). Addition of epinephrine to the bupivacaine eliminated the protective effect of propranolol. All rats pretreated with propranolol (Group III) or NS (Group IV) died when given bupivacaine with epinephrine. In conclusion, acute propranolol pretreatment reduced the fatal cardiotoxicity due to iv bupivacaine in male Sprague Dawley rats, but the addition of epinephrine 5 μg · ml^{? 1} to bupivacaine eliminated the protective effect of propranolol.     

Effect of normal and preeclamptic pregnancies on the oxyhemoglobin dissociation curve

Hemoglobin affinity for oxygen in whole blood of ten normal nonpregnant women, ten normal pregnant women at first trimester, ten normal pregnant women at second trimester, 24 normal pregnant women at or near term, and 14 pregnant women with preeclampsia at or near term was studied. The mean P-50 values for normal nonpregnant women, normal pregnant women in first trimester, second trimester, and at or near term were 26.7 +/- 0.11 mmHg, 27.8 +/- 0.08 mmHg, 28.8 +/- 0.17 mmHg, and 30.4 +/- 0.20 mmHg, respectively. The mean P-50 of pregnant women with preeclampsia at or near term was 25.1 +/- 0.38 mmHg. It is concluded that in normal pregnant women there was a significant shift of P-50 to the right compared with the normal nonpregnant women (P less than 0.01), and the extent of this shift to the right is directly related to the duration of the pregnancy. In addition, preeclamptic parturients showed a significant shift of P-50 to the left when compared with normal pregnant women at or near term (P less than 0.001).     

Effect of nitrous oxide on the oxyhemoglobin dissociation curve and PO2 measurements

Blood from 20 ASA physical status I patients collected before and after induction of anesthesia was used in vitro to reexamine the effects of nitrous oxide on the oxyhemoglobin dissociation curve and the response of the oxygen electrode. The preinduction P50 values with and without 70% N2O were 28.4 +/- 0.1 mmHg and 26.8 +/- 0.1 mmHg, respectively. The postinduction P50 values with and without N2O were unchanged, namely 28.4 +/- 0.1 mmHg and 26.8 +/- 0.1 mmHg, respectively. Our data confirm the observation that N2O causes a small elevation of P50 (P less than 0.001) and that this effect is both rapidly inducible and reversible. Our results also indicate that N2O has no effect on polarographic PO2 measurements.     

Intrapleural analgesia for postthoracotomy pain and blood levels of bupivacaine following intrapleural injection

An epidural type catheter was placed in the pleural space under direct vision before the closure of the chest in 24 patients who underwent thoracotomy for various types of lung or aortic surgery. All patients received intrapleural injections of 20 ml of 0.5 per cent bupivacaine with or without epinephrine as initial pain therapy. Patients also received subsequent doses of a similar volume of 0.375 per cent bupivacaine with epinephrine 1:200,000 up to four times a day for a maximum duration of seven days. Good pain relief was achieved in patients who underwent lateral and posterior thoracotomies. No pain relief was achieved in patients who underwent anterior thoracotomy or in patients in whom there was excessive bleeding in the pleural space. Bupivacaine blood concentrations were measured in 11 patients following the initial dose of 20 ml of 0.5 per cent bupivacaine (with epinephrine 1:200,000 in five of the 11 patients). The mean peak plasma concentration of bupivacaine when used with epinephrine was 0.32 +/- 0.02 microgram.ml-1. The mean peak plasma concentrations of bupivacaine when used without epinephrine was 1.28 +/- 0.48 microgram.ml-1. Our present data show that intrapleural analgesia is useful in the management of postoperative pain in patients who undergo thoracotomy. Our data also show that there is a significant decrease in peak plasma concentrations of bupivacaine when epinephrine is added to the solution (P less than 0.05).     

Cimetidine-carbaryl interaction in humans: evidence for an active metabolite of carbaryl.

The influence of cimetidine on the pharmacokinetic and pharmacodynamic response to the insecticide carbaryl has been investigated in isolated human erythrocytes (red blood cells; RBC) and after oral administration of 1 mg/kg carbaryl to four normal subjects in the absence or presence of cimetidine (300 mg, 8/hr for 3 days). Carbaryl induced a concentration-dependent reduction of isolated RBC acetylcholinesterase activity requiring 1 microgram/ml to achieve 20% inhibition. Cimetidine also induced a dose-dependent inhibition of RBC acetylcholinesterase activity, but at 40-fold higher concentrations. At high concentrations, cimetidine was additive to carbaryl-induced inhibition of RBC acetylcholinesterase, but exhibited no effect at the therapeutically relevant concentrations (10 micrograms/ml). After oral carbaryl administration to normal subjects, plasma concentrations rapidly rose to a peak, then declined with a half-life of 0.79 +/- 0.47 hr. Oral carbaryl clearance was 5.4 +/- 2.0 l/min. Peak plasma carbaryl concentrations were associated with 27% inhibition of RBC acetylcholinesterase activity, and the concentration associated with a reduction of RBC acetylcholinesterase activity of 20% was 0.02 microgram/ml. The terminal half-life for the dynamic response was 2.6 +/- 1.5 hr. After pretreatment with cimetidine, peak plasma carbaryl concentrations doubled and clearance was reduced (to 2.5 +/- 1.5 l/min) (P less than .05). However, half-life remained unchanged. Despite increased carbaryl levels, the maximum inhibition of RBC acetylcholinesterase activity was significantly reduced, and the concentration of carbaryl required to achieve 20% inhibition of RBC acetylcholinesterase activity was increased to approximately 0.5 microgram/ml. These results are consistent with the hypothesis that carbaryl is metabolized by drug-metabolizing enzymes that can be inhibited by cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)