Mark Tverskoy

Postoperative Pain After Inguinal Herniorrhaphy with Different Types of Anesthesia

In a randomized, double-blind study, postoperative pain was assessed in 36 patients undergoing inguinal herniorrhaphy with three types of anesthesia: general (thiopental-nitrous oxide-halothane); general with the addition of local (infiltration of the abdominal wall with 0.25% bupivacaine along the line of the proposed incision); and spinal (0.5% bupivacaine). The severity of constant incisional pain, movement-associated incisional pain, and pain upon pressure applied to the surgical wound using an algometer was assessed with a visual analogue self-rating method at 24 h, 48 h, and 10 days after surgery. The addition of local anesthesia significantly decreased the intensity of all types of postoperative pain. This effect was especially evident with constant incisional pain that disappeared almost completely 24 h after surgery. With pain caused by pressure on the site of the surgical incision, the pain score difference between general and general plus local anesthesia was obvious even 10 days after the surgery (with 0.4-kg/cm2 pressure, the pain scores were 16 ± 3 vs 2 ± 1, P < 0.01). The difference in postoperative pain scores between spinal and general anesthesia groups indicated that spinal anesthesia also decreases the pain intensity. However, this decrease is less pronounced than that seen with the addition of local anesthesia: movement-associated pain scores 24 h after surgery were 72 ± 5 in the general anesthesia group, 40 ± 6 in the spinal anesthesia group, and 16 ± 3 in the general plus local anesthesia group (with P < 0.002 between the groups).Our results indicate that postoperative pain after inguinal herniorrhaphy can be significantly decreased if the surgery is performed with the use of local or spinal anesthesia. We hypothesize that neural blockade, by preventing nociceptive impulses from entering the central nervous system during and immediately after surgery, suppresses the formation of the sustained hyperexcitable state in the central nervous system that is responsible for the maintenance of postoperative pain.

PREEMPTIVE EFFECT OF FENTANYL AND KETAMINE ON POSTOPERATIVE PAIN AND WOUND HYPERALGESIA

The aim of this study was to test the hypothesis that the induction and maintenance of anesthesia with the use of fentanyl or ketamine reduces postoperative pain and wound hyperalgesia beyond the period when these effects can be explained by the direct analgesic action of these drugs. Twenty-seven patients scheduled for elective hysterectomy were investigated in a double-blind, randomized study. Patients were divided into three groups. In the fentanyl group, anesthesia was induced with fentanyl 5 micrograms/kg combined with thiopental 3 mg/kg and maintained with isoflurane and fentanyl 0.02 microgram.kg-1.min-1. In the ketamine group, anesthesia was induced with ketamine 2 mg/kg in combination with thiopental 3 mg/kg and maintained with isoflurane and ketamine 20 micrograms.kg-1.min-1. In the control group, anesthesia was induced with thiopental 5 mg/kg and maintained with isoflurane only. Patients in all three groups received identical postoperative pain treatment. The intensity of spontaneous incisional pain and movement-associated pain was measured with a visual analog self-rating method. The surgical wound hyperalgesia was assessed by measuring pain threshold to pressure on the wound by using an algometer, and also by measuring the intensity of pain to suprathreshold pressure on the wound with the visual analog self-rating method. Forty-eight hours after surgery, the pain threshold was 0.90 +/- 0.06 kg in controls, 1.69 +/- 0.19 kg (P < 0.001) in the fentanyl group, and 1.49 +/- 0.15 kg (P < 0.01) in the ketamine group.(ABSTRACT TRUNCATED AT 250 WORDS)

Ketamine enhances local anesthetic and analgesic effects of bupivacaine by peripheral mechanism: a study in postoperative patients.

Patients with unilateral (n = 14) and bilateral (n = 4) herniorrhaphy participated in this study. With bilateral herniorrhaphy, at the end of the surgery, the wound was infiltrated with a solution of bupivacaine 0.5% and ketamine 0.3% on one side and a solution of bupivacaine 0.5% only, on the other. With unilateral herniorrhaphy, the patients were randomly assigned to one of two groups (n = 7). One group at the end of the surgery received the infiltration with a solution of bupivacaine 0.5% and ketamine 0.3%, the other group received the infiltration with a solution of bupivacaine 0.5% only. The duration of the local anesthetic (response to a von Frey filament) and postoperative analgesic (time to mild spontaneous pain) effects of the infiltrations, as well as wound pain threshold 24 h after surgery (pressure algometry), were determined. In patient with unilateral herniorrhaphy, the addition of ketamine for wound infiltration enhanced the duration of infiltration anesthesia (206 +/- 76 versus 343 +/- 108 min, P < 0.02) and analgesia (240 +/- 45 versus 420 +/- 151 min, P < 0.03). Similar enhancement of the local anesthetic effect was observed in patients with bilateral herniorrhaphy. The increase in pain threshold to pressure on the wound with the addition of ketamine was evident in bilateral herniorrhaphy patients and also with a combination of bilateral and unilateral results (1.39 +/- 0.40 versus 2.35 +/- 0.92 kg, P < 0.02). In the group of five volunteers, the subcutaneous infiltration with 0.3% ketamine produced a local anesthetic effect lasting only 10-20 min. The results indicate that ketamine acting via a peripheral mechanism can profoundly enhance anesthetic and analgesic actions of a local anesthetic administered for infiltration anesthesia.

Subarachnoid bupivacaine blockade decreases midazolam and thiopental hypnotic requirements

STUDY OBJECTIVE To test the hypothesis that subarachnoid bupivacaine blockade decreases hypnotic requirements for thiopental sodium and midazolam. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Teaching hospital. PATIENTS 53 nonpremedicated ASA physical status I and II adult male patients scheduled for elective lower abdominal, pelvic, or lower limb surgery. INTERVENTIONS Intravenous injections of midazolam or thiopental were administered with or without subarachnoid bupivacaine blockade (12.5 mg) at the L3-L4 level. Thiopental or midazolam hypnotic requirements were determined using loss of ability to open eyes in response to verbal command as an endpoint. The thiopental requirements were determined by titration; the midazolam requirements were determined from dose-response curves obtained with bolus injections of predetermined doses of the drug. MEASUREMENTS AND MAIN RESULTS Subarachnoid bupivacaine blockade decreased the hypnotic dose of thiopental from 3.40 +/- 0.68 mg/kg (mean +/- SD) with a dose range of 2.3 to 4.5 mg/kg (intramuscular saline) to 2.17 +/- 0.48 mg/kg with a dose range of 1.3 to 2.8 mg/kg (p < 0.005 for the difference). The ED50 value of midazolam decreased with the bupivacaine blockade, from 0.23 mg/kg (95% confidence limits: 0.08 to 0.38 mg/kg) to 0.06 mg/kg (0.01 to 0.14 mg/kg), with p < 0.0001 for the difference. CONCLUSION Subarachoid bupivacaine blockade decreases hypnotic requirements for both thiopental and midazolam. The results suggest that the reduction in hypnotic requirements is due to the decrease in afferent input induced by spinal anesthesia.

Midazolam-Thiopental Anesthetic Interaction in Patients

The effect of thiopental on the induction dose-response curve for midazolam was studied innonpremedicated ASA physical status I and II patients. As an endpoint of anesthesia, ability to open eyes on command was used. Dose-response curves for thiopental, midazolam, and their combination were determined with a probit procedure and compared with an isobolographic analysis. Interaction between midazolam and thiopental was found to be synergistic (supraadditive). The degree of midazolam-thiopental anesthetic synergism in surgical patients was close to that reported previously in rats with loss of the righting reflex as an index of anesthesia.

Midazolam-morphine sedative interaction in patients.

The sedative effects of midazolam, morphine, and their combination were studied in ASA physical status I and II patients. The visual analog method was used to determine sedative effect. A self-rated score of 50 mm or more on a 100-mm line was regarded as a positive response to the treatment. The dose-response curves for midazolam, morphine, and their combination (each in a group of 30 patients) were determined by probit procedure and compared with isobolographic and algebraic (fractional) analyses. Interactions between midazolam and morphine when used to produce sedation represent summation, not synergism.

Intestinal circulation during inhalation anesthesia.

This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86Rb and 9-μm spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P < 0.0001), suggesting that the shunting of 9-μm spheres through the intestines reflects the arteriovenous shunting of blood. Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO2) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. α-Adrenoceptor blockade with phentolamine (1 mg·kg−1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines. Decreases in mesenteric blood flow, which always have been observed during inhalation anesthesia, primarily are caused by the indirect effects of anesthetics mediated through changes in systemic circulation and the central nervous system.

The Peripheral Effect of Fentanyl on Postoperative Pain

The clinical value of the analgesic effect of opioids administered peripherally (except for intraarticular administration) has not been clearly demonstrated.The aim of this study was to test the hypothesis that fentanyl, added to a local anesthetic for wound infiltration, can enhance postoperative analgesia via a peripheral mechanism. Patients with inguinal herniorrhaphy performed under spinal anesthesia were randomly assigned to one of two groups (n = 10 each). At the end of surgery, the wound was infiltrated with 10 mL of lidocaine 0.5% and fentanyl 0.001% (10 [micro sign]g) in one group; in the other group, the wound was infiltrated with 10 mL of lidocaine 0.5% alone (and fentanyl 10 [micro sign]g IM contralaterally). The following variables were determined in a double-blind manner: the duration of anesthesia (response to a von Frey filament), the duration of analgesia (time to mild postoperative pain), postoperative meperidine consumption, intensity visual analog scale of spontaneous and movement-associated pain 24 h after surgery, and wound pain threshold 24 h after surgery (pressure algometry). The addition of fentanyl for wound infiltration enhanced the duration of anesthesia (130 +/- 37 vs 197 +/- 27 min; P < 0.001) and decreased the intensity of spontaneous (50 +/- 17 vs 19 +/- 18 mm; P < 0.002) and movement-associated (56 +/- 15 vs 26 +/- 21 mm; P < 0.002) pain 24 h postoperatively. Differences between groups for other variables were not statistically significant. Fentanyl added to a local anesthetic for wound infiltration after spinal anesthesia can enhance postoperative analgesia by a peripheral mechanism. Implications: Fentanyl can enhance analgesia by a peripheral mechanism. Added to a local anesthetic for wound infiltration, it may be of benefit for the relief of postoperative pain. (Anesth Analg 1998;87:1121-4)

Influence of fentanyl and morphine on intestinal circulation

The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of 86Rb and 9-μm spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P < 0.0001), suggesting that the shunting of 9-μm spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O2up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg·kg−1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg·kg−1 was accompanied by vasoconstriction that was completely abolished by α-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from theadrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation.

Effects of anaesthesia induction drugs on circulation in denervated intestinal loop preparation.

The effect of anaesthesia induction drugs on the intestinal circulation was evaluated in an isolated loop preparation in 28 dogs. Selected intestinal loops were perfused with aortic blood by a pump at a constant pressure of 100 mmHg. A mixture of86Rb and 9 μn spheres labeled with141Ce was injected into the arterial cannula supplying the intestinal segment while mesenteric venous blood was collected for activity counting. Diazepam in a dose of 3 mg·kg-1 was accompanied by a significantly lower clearance (Cl-Rb), and permeability-surface area product (PS) than pentobarbitone; there were no differences between diazepam and pentobarbitone in total blood flow (BF), vascular resistance (VR) and oxygen consumption in the intestinal segments. Circulatory variables observed after midazolam, 8mgμkg-1 and an additional 16mgμkg-1, did not significantly differ from those seen during pentobarbitone. Ketamine in a dose of 8 mgμkg-1 was accompanied by a significantly lower BF, Cl-Rb, microsphere entrapment (Cl-Sph), PS, and higher VR and arterio-venous oxygen content difference. Sixteen mgμkg-1 of ketamine did not lead to any additional changes in determined variables of the intestinal circulation. Alpha-adrenoceptor blockade completely abolished vasoconstriction caused by ketamine, suggesting that the long-lasting vasoconstricting effect of ketamine on the intestinal circulation is mediated through catecholamines.RésuméLes effets des agents anesthésiques utilisés lors de I’induction sur la circulation intestinale ont été évalués chez 28 chiens utilisant une préparation où un circuit intestinal est isolé. Les circuits d’intestin choisis ont été perjusés avec du sang aortique utilisant une pompe à pression constante de 100 mmHg. Un mélange de Rb86 et des microsphères de 9 µm marqués avec du Ce 141 ont été injectés dans la canule artérielle nourissant le segment intestinal alors que le sang veineux mésentérique a été recueilli afin de mesurer la radioactivité résiduelle. Le diazepam à des doses de 3 mg-kg-1 a démontré une clairance de rubidium (Cl-Rb) et un produit surface-perméabilité (PS) significativement plus bas que le pentobarbitone. II n’y avait aucune différence entre le diazepam et le pentobarbitone quant au flot sanguin total (BF), résistance vasculaire (VR) et consommation d’oxygene des segments d’intestin. Les perturbations de la circulation observé.es après midazolam, 8 mg.kg-1 et une dose additionnelle de 16 mg-kg-1 n’etaient pas significativement différentes de celles observées lors de I’induction avec le pentobarbitone. La ketamine à des doses de 8mg-kg-1 était accompagnée par un Cl-Rb, un BF, une capture de microsphères (Cl-Sph), un PS, significativement plus bas. La VR et la différénce artério-veineuse du contenu en oxygène étaient plus hautes. 16mgkg-1 de ketamine n’ont pas amené des changements additionnels dans les variables étudiées. Un blocage des récepteurs alpha-adrénergiques a complètement aboli la vasoconstriction causée par la ketamine suggérant que I’effet vasoconstricteur de la ketamine est dû aux catécho-lamines.