J. Reddy Kambam

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 μg·ml-1. The mean peak plasma concentrations of bupivacaine when used without epinephrine was 1.28 ± 0.48 μg·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 < 0.05).RésuméChez 24 patients, lors ďune thoracotomie pour chirurgie aortique ou pulmonaire, nous avons laissé un cathéter de type épidural dans la cavité pleurale. A titre ďanalgésique, nous y avons ďabord injecté 20 ml de bupivacaine 0.5 pour cent avec ou sans adrénaline 1.200,000. Nous avons poursuivi la thérapie à raison de doses de 20 ml de bupivacaine 0.375 pour cent avec adrénaline 1:200,000 injectées jusqu’à quatre fois par jour durant un maximum ďune semaine. Ľanalgésie s’est avérée adéquate dans les cas de thoracotomies postérieures ou latérales mais insuffisante pour les thoracotomies antérieures ou en présence ďhémorragie intrapleurale. Après la première dose de 20 ml de bupivacaine 0.5 pour cent, nous en avons mesuré les taux sériques chez 11 patients (dont cinq avaient de ľadrénaline 1:200,000 mélangée à ľanesthésique local). Administrée seule, la bupivacaine atteignait un taux sérique maximal moyen de 1.28 ± 0.48 μg·ml-1 alors que ľadjonction ďadrénaline réduisait cette valeur à 0.32 ± 0.02 μg·ml-1 (P < 0.05). En postopératoire ďune thoracotomie, ľanalgésie intra-pleurale s’avàre utile et ľaddition ďadrénaline à la bupivacaine en réduit le taux sérique maximal.

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).

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.RésuméEn chirurgie cardiovasculaire on utilise souvent de la protamine, un composé polycationique alcalin, en tant qu’ antidote à l’ anticoagulation de l’ héparine. L’ usage de la protamine peut causer diverses réactions telles que: hypotension légère, vasoconstriction pulmonaire marquée, hypoxémie et choc anaphylactoïde.1–4D’aucuns croient que ces complications peuvent être expliquées par la libération d’histamine par des mastocytes mis en contact avec la protamine. Transmetteur par excellence des réactions allergiques, l’ histamine agit sur deux types de récepteurs, H1 et H2. Certains des effets hémodynamiques de l’ histamine peuvent être contrés par des antagonistes des récepteurs H1, mais le rôle des anti-H2 dans le traitement des reactions anaphylactoïdes n’a pas encore été établi. Avec la protamine, deux de nos patients ont eu une réaction anaphylactoide résistante à la thérapie suivante: hydratation intraveineuse, adrénaline, diphenhydramine, chlorure de calcium et stéroïdes. Nous avons alors injecté de la cimétidine, un anti-H2, qui a rapidement corrigé le problème.

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.

Pseudocholinesterase activity in human cerebrospinal fluid

Pseudocholinesterase (PCHE) activity and dibucaine numbers (DN) in the cerebrospinal fluid (CSF) and plasma of 10 ASA physical status 1 and 2 patients were measured using a kinetic method. CSF had a mean PCHE activity of 0.018 +/- 0.013 unit/ml with a DN of 59 +/- 4. Whereas, PCHE activity and DN in the plasma were 0.960 +/- 0.12 units/ml and 84 +/- 3, respectively. We also measured PCHE activity and DN in the CSF and plasma of 4 patients in whom there was a recent history of intraventricular bleeding. These patients had a CSF PCHE activity of 0.340 +/- 0.07 units/ml (DN = 78 +/- 3) and a plasma PCHE activity of 0.950 +/- 0.10 units/ml (DN = 82 +/- 2). Our data show that there is a low activity of PCHE in CSF, 1/20-1/100th that of plasma. Our data also show that PCHE activity increased to 1/4 to 1/2 that of plasma in CSF of patients with bleeding into CSF.

Effect of pre-eclampsia on plasma cholinesterase activity

RésuméOn a déterminé ľactivité de la cholinestérase plasmatique chez 11 femmes en santé, 11 femmes en santé étant au terme de leur grossesse, et 11 femmes prééclamptiques étant au terme de leur grossesse, en utilisant une méthod colorimétrlque. Ľactivité moyenne de la cholinestérase plasmatique pour les femmes en samé, les femmes enceintes en santé et les femmes enceintes préédamptiques élait de438 ± 81,257 ± 25 et 173 ± 18 unites par ml, respectivement. Nos données laissent entendre que ľactivité de la cholinestérase plasmatique est réduite de façon significative chez les femmes enceintes préédamptiques en comparaison à celle des femmes en santé (p < 0.001) et à celle des femmes enceintes en santé (p < 0.001).

The inhibitory effect of metoclopramide on plasma cholinesterase activity

The in vitro effect of metoclopramide on plasma cholinesterase (PCHE) activity was studied to investigate a mechamistn for metoclopramide-induced prolongation of succinylcholine action. The mean PCHE of the control samples was 0.86 ° 0.02 unit·ml-1. PCHE activity in the presence of metoclopramide, at concentrations of 0.05, 0.10, 0.50,1.0, 2.5 and 5.0 μg·ml-1, was reduced to 0.78 ± 0.02, 0.69 ± 0.04,0.50 ± 0.03,0.39 ± 0.02, 0.24 ± 0.01 and 0.15 ± 0.01 unit ·ml-1, respectively. Our data demonstrated that PCHE activity was significantly depressed by metoclopramide at all concentrations studied (p < 0.001). Our data also show that the concentration of metoclopramide required to inhibit 50 per cent of PCHE activity (I50) was 0.8 μg·ml-1 (2.4 × 10-6 M). We recommend caution when succinylcholine and or ester type local anaesthetics are administered to patients who are also receiving metoclopramide, especially in high doses.RésuméĽeffet in vitro de la métoclopramide sur ľactivité de la cholinestérase plasmatique (PCHE) a été étudié afin ďinvestiguer le mécanisme de la prolongation de ľaction de la succinylcholine induite par la métoclopramide. La valeur moyenne des échantillons de contrôle de PCHE était de 0.86 ± 0.02 unités · ml-1. Ľactivité du PCHE en présence de métoclopramide à des concentrations de 0.05, 0.10, 0.50,1.0. 2.5 et 5.0 μg·ml-1, a été réduiteà0.78 ± 0.02, 0.69 ± 0.04, 0.50 ± 0.03, 0.39 ± 0.02, 0.24 ± 0.01 et 0.15 ± 0.01 unités·ml-1 respectivement. Nos données ont démontré que ľactivité de la PCHE était significativement diminuée par la métoclopramide à toutes les concentrations étudiées (p < 0.001). Nos données ont aussi démontré que la concentration de métoclopramide requise afin ďinhiber 50 pour cent de ľactivité de la PCHE (150) était de 0.8 μg · ml-1 (2.4 × 10-6 M). On recommande la précaution quand la succinylcholine ou anesthésique local type ester est administré aux patients qui reçoivent aussi la métoclopramide, spécialement à hautes doses.

The effect of procainamide on plasma cholinesterase activity

The in vitro effect of procainamide on plasma cholinesterase (PCHE) activity in the plasma often normal ASA physical status I patients was studied using a kinetic method. The mean plasma cholinesterase activity without procainamide (control) was 0.90 ± 0.09 units.ml-1 The dibucaine numbers of all the samples were in the normal range of 78 to 86, indicating normal genotypes. The mean plasma cholinesterase activity, in the presence of procainamide in concentrations of 5.0, 10.0, 20.0 and 40.0 µ.ml-1, was reduced to 0.73 ± 0.04. 0.61 ± 0.03, 0.45 ± 0.02, and 0.36 ± 0.01 units.mt-1, respectively. At therapeutic concentrations of 4 to 12 µg.ml-1, procainamide inhibited cholinesterase activity 15 to 30 per cent. The authors also showed that the concentration of procainamide required to inhibit 50 per cent of plasma cholinesterase activity was 20 µg.mt-1 (Iso). The authors conclude that procainamide when tested in vitro had a statistically significant depressant effect on plasma cholinesterase activity at all the concentrations studied.RésuméOn a étudié ľeffet in vitro de la procaïnamide sur ľactivité de la cholinestérase plasmatique (PCHE) dans le plasma de dix patients normaux de statut physique ASA I, à ľaide ďune méthode cynétique. Ľactivité de la cholinestérase plasmatique moyenne sans procainamide (groupe témoin) était de 0.90 ± 0.09 unités.ml-1. Les nombres de dibucaine, pour tous les échantillons, se situaient dans ľéchelle normale de 78 à 86 dénotant, de ce fait, des génotypes normaux. La présence de procainamide dans des concentrations de 5.0, 10.0, 20.0 et 40.0 µg.ml-1, réduisait ľactivité de la cholinestérase plasmatique moyenne à 0.73 ± 0.04, 0.61 ± 0.03, 0.45 ± 0.02, et 0.36 ± 0.01 unités.ml-1, respectivement. Des concentrations thérapeutiques de 4 à 12 µg.ml-1 de procaïnamide inhibaient ľactivité de la cholinestérase de 15 à 30 pour cent. Les auteurs ont aussi démontré que la concentration de procaïnamide requise pour inhiber 50 pour cent de ľactivité de la cholinestérase plasmatique était de 20 µg.ml-1 (I50). Les auteurs concluent que la procaïnamide testée in vitro a un effet dépressif statistiquement significatif sur ľactivité de la cholinestérase plasmatique à toutes les concentrations étudiées.

Inhibitory effect of quinidine on plasma pseudocholinesterase activity in pregnant women

The effect of quinidine at therapeutic and subtherapeutic concentrations on pseudocholinesterase activity in the plasma of 16 normal pregnant women was studied. The mean plasma pseudocholinesterase activity in the absence of quinidine (control) was 0.67 +/- 0.11 U/ml. The mean pseudocholinesterase activity in the presence of quinidine at concentrations of 0.5, 1.0, 2.0, and 5.0 micrograms/ml 0.48 +/- 0.09, 0.38 +/- 0.09, 0.29 +/- 0.10, and 0.19 +/- 0.09 U/ml, respectively. At therapeutic concentrations needed to treat cardiac arrhythmias (2 to 5 micrograms/ml), quinidine inhibited pseudocholinesterase activity by 60% to 70%. All the plasma samples had a normal dibucaine number (78 to 85). We recommend caution when succinylcholine and/or ester-type local anesthetics are used in pregnant women receiving quinidine.

Effect of preeclampsia on carboxyhemoglobin levels: a mechanism for a decrease in P50

COHb levels were measured in 15 preeclamptic pregnant women and 15 normal pregnant women to investigate the cause for the decrease in P50 associated with preeclampsia. The authors also included six normal and six preeclamptic pregnant patients from the above groups in the determination of P50. Measurements of COHb levels were performed in a Radiometer OSM2 Hemoximeter. Determination of P50 was done using an IL 237 Tonometer, a Radiometer, OSM2 Hemoximeter, and a Corning 168 pH/Blood Gas Analyzer. Preeclamptic pregnant patients had a mean COHb level of 2.8%, whereas normal pregnant women had a mean COHb level of 0.7% (P less than 0.001). Preeclamptic patients also had a significantly lower (24.4 mmHg) P50 than normal pregnant women (P50 = 30.1 mmHg) (P less than 0.001). The authors conclude that a significant elevation of COHb in preeclamptic pregnant women is partly responsible for a significant decrease in P50 seen in preeclampsia.