Adolph H. Giesecke

Ketamine suppresses endotoxin-induced NF-κB expression

Purpose: Ketamine reduces endotoxin-induced production of proinflammatory cytokines, including tumour necrosis factor- α (TNF), in several types of inflammatory cells, including monocytes and macrophages. Transcription of the genes that encode production of these proinflammatory cytokines is regulated by nuclear factor-kappa B (NF-κB). Cytoplasmic B protein is activated by endotoxin (LPS) as well as by TNF, allowing B protein to migrate into the cell nucleus to activate gene transcription for these inflammatory mediators. Because NF-κB is likely involved in brain injury and inflammatory neurodegenerative disease, such as multiple sclerosis, we examined whether ketamine inhibits LPS-induced activation of NF-κB in human glioma cellsin vitro and intact mouse brain cellsin vivo.Methods: Endotoxin-induced NF-κB expression in both the human glioma cellsin vitro and the intact mouse brain cellsin vivo was determined by electrophoretic mobility shift assays (EMSA) of nuclear extracts and measurement of NF-κB expression by densitometry. Endotoxin was injected intracerebroventricularlyin vivo and intact brain was harvested. Klenow fragment labeling was used to identify NF-κB protein for both thein vivo andvitro experiments.Results: Endotoxin treatment increased NF-κB expression (P<0.05) bothin vivo andvitro compared with control (untretaed) cells. Ketamine suppressed endotoxin-induced neuronal NF-κB activation in a dose-dependent manner (P<0.05, except for the 10−5M concentrationin vitro) bothin vivo andvitro.Conclusion: Ketamine inhibits endotoxin-induced NF-κB expression in brain cellsin vivo andvitro and it is suggested that this may have implications in the neuroprotective effects of ketamine reported by other investigators.RésuméObjectif: La kétamine réduit la production de cytokines pro-inflammatoires induite par endotoxine, y compris le facteur nécrosant des tumeurs (TNF), dans certains types de cellules inflammatoires comprenant les monocytes et les macrophages. La transcription des gènes qui encodent la production de ces cytokines pro-inflammatoires est réglée par le facteur-kappa B nucléaire (NF-6B). La protéine cytoplasmique 6B est activée par l’endotoxine (LPS) et par le TNF et peut ainsi migrer dans le noyau cellulaire et activer la transcription génique pour ces médiateurs de l’inflammation. Comme le NF-6B participe probablement aux lésions cérébrales et aux maladies inflammatoires neurodégénératives, dont la sclérose en plaques, notre but était de savoir si la kétamine inhibe l’activation de NF-6B induit par LPS dans des cellules de gliome humainin vitro et dans des cellules cérébrales intactes de sourisin vivo.Méthode: L’expression du NF-6B induite par endotoxine dans les cellules humainesin vitro et dans les cellules de sourisin vivo a été déterminée par une étude de retardement de la mobilité électrophorétique (ERME) d’extraits nucléaires et la mesure de l’expression du NF-6B a été faite par densitométrie. L’endotoxine a été injectée dans les ventricules cérébrauxin vivo et du tissu cérébral intact a été prélevé. Le marquage de fragments de Klenow a été utilisé pour identifier la protéine du NF-6B des deux expériencesin vivo etvitro.Résultats: Le traitement avec l’endotoxine a augmenté l’expression du NF-6B (P<0,05) des cellulesin vivo etin vitro comparées aux cellules témoin (non traitées). La kétamine a supprimé l’activation neuronale de NF-6B induite par endotoxine d’une façon dose-dépendante (P<0,05, sauf pour une concentration de 10−5Min vitro) des cellulesin vivo etin vitro.Conclusion: La kétamine inhibe l’expression de NF-6B induite par endotoxine dans des cellules cérébralesin vivo etin vitro et on croit que cela pourrait contribuer aux effets neuroprotecteurs de la kétamine dont parlent d’autres chercheurs.

Intrathecal fentanyl prolongs sensory bupivacaine spinal block

The purpose of investigation was to study the effect of intrathecal fentanyl on the onset and duration of hyperbaric bupivacaine-induced spinal block in adult male patients. Fortythree patients undergoing lower extremity or genitourinary surgery were enrolled to receive either 13.5 mg hyperbaric bupivacaine 0.75% + 0.5 ml CSF it, (Group I) or 13.5 mg hyperbaric bupivacaine 0.75% + 25 μg fentanyl it, (Group II) according to a randomized assessor-blind protocol. The onset and duration of sensory block were assessed by pinching the skin with forceps in the midclavicular line bilaterally every two minutes for first twenty minutes and then every five to ten minutes. Similarly, the onset and duration of motor block were assessed and graded at the same time intervals using the criteria described by Bromage. The time required for two sensory segment regression and sensory regression to L1 dermatome was 74 ± 18 and 110 ± 33 min vs 93 ± 22 and 141 ± 37 min in Groups I and II, respectively (P < 0.05). Intrathecal fentanyl did not enhance the onset of sensory or motor block, or prolong the duration of bupivacaine-induced motor spinal block. Fewer patients demanded pain relief in the fentanyl-treated group than in the control group in the early postoperative period (19% vs 59%; P < 0.05). Episodes of hypotension were more frequent in the fentanyl-treated group than in the control group (43% vs 14%; P < 0.05). We conclude that fentanyl, 25 μg it, prolonged the duration of bupivacaine-induced sensory block (sensory regression to L1 dermatone) by 28% and reduced the analgesic requirement in the early postoperative period following bupivacaine spinal block.RésuméCette étude a pour objectif d’examiner l’effet du fentanyl sousarachnoïdien sur le début et la durée de la rachianesthésie hyperbare à la bupivacaïne chez des patients adultes de sexe masculin. Quarante-trois patients opérés sur une extrémité inférieure ou sur l’appareil génito-urinaire sont répartis pour recevoir au hasard en rachianesthésie soit 13,5 mg de bupivacaïne hyperbare à 0,75% avec 0,5 ml de LCR (groupe I), soit 13,5 mg de bupivacaïne hyperbare à 0,75% avec 25 μg de fentanyl (groupe II). Le debut et la durée du bloc sont évalués en coinćant la peau avec une pince sur la ligne médioclaviculaire bilatéralement à toutes les deux minutes pour les 20 premières minutes et à toutes les cinq à dix minutes par la suite. En même temps, le début et la durée du bloc moteur sont évalués et classé aux mêmes intervalles selon les critères de Bromage. Le temps requis pour la regression de deux segments sensoriels et la régression sensorielle jusqu’au dermatome de L1 est de 74 ± 18 et 110 ± 33 vs 93 ± 22 et 141 ± 37 min dans les groupes I et II respectivement (P < 0,05). Le fentanyl sousarachnoïdien n’accélère pas le début des blocs sensoriel et moteur ni ne prolonge la durée du bloc moteur produit par la bupivacaïne. Moins de patients ont demandé un analgésique dans le groupe fentanyl que dans le groupe contrôle à la période postopératoire immédiate (19% vs 59% P < 0,05). Les épisodes d’hypotension sont plus fréquents dans le groupe traité au fentanyl que dans le groupe contrôle (43% vs 14%, P < 0,05). Les auteurs concluent que le fentanyl 25 μg sous-arachoïdien prolonge la durée du bloc senstif induit par la bupivacaïne (mesurée par la régression au dermatome de L1) par 28% et diminue les besoins en analgésie dans le période postopératoire immédiate après une rachianesthésie.

Relationship between diabetic autonomic neuropathy and gastric contents.

Delayed gastric emptying secondary to diabetic autonomic neuropathy (DAN) is a recognized risk factor for aspiration pneumonitis. The purpose of this study is to determine whether bedside autonomic function tests (AFTs) would predict gastric contents. Gastric volume and its pH were measured in 36 patients with diabetes mellitus (DM) and 15 nondiabetic patients at induction of general anesthesia for elective ambulatory surgery. Manifestations of autonomic dysfunction were assessed preoperatively in all 51 patients with five commonly used cardiovascular AFTs. According to the results of these five tests, 16 patients with DM met the criteria for the diagnosis and are called “DAN positive.” The remaining 20 diabetics did not meet the criteria and are called “DAN negative.” Fifteen patients without DM did not meet the criteria and are called “nondiabetics.” Diabetic patients were significantly older and more obese than nondiabetics and those with DM more than 10 yr were more often DAN positive. Solid, undigested food particles were found more often in the gastric contents of DAN-positive patients compared to nondiabetics. Gastric liquid volume and pH were similar in diabetic patients (DAN positive and DAN negative) and nondiabetic controls. These results demonstrate that diagnosis of DAN by commonly used cardiovascular AFTs does not predict larger gastric liquid volume or lower pH, but does predict the presence of solid food particles. The presence of food particles in gastric contents after 8 h of fasting could represent a risk factor for aspiration pneumonitis. Autonomic neuropathy is not manifested equally in the cardiovascular and gastrointestinal systems, but may be more severe in one than the other.

Low-dose synthetic narcotic infusions for cerebral relaxation during craniotomies.

Thirty patients undergoing craniotomies were given infusions of fentanyl 1 μg·kg 1·hr 1, sufentanil 0.1 μg·kg−1·hr−1 or normal saline in a double-blind study of cerebral relaxation. Significantly better relaxation scores were achieved in patients given a narcotic infusion, but there was no difference between the scores with the two narcotics. Infusions of narcotics at these low rates did not delay recovery or alter the requirement for other anesthetic agents. Narcotic infusion rates that do not delay recovery or alter depth of anesthesia significantly improve cerebral relaxation.

Perioperative measurements of interleukin-6 and α-melanocyte-stimulating hormone in cardiac transplant patients

Interleukin-6 (IL-6) and alpha-melanocyte-stimulating hormone (alpha MSH) are important modulators of the immunologic response to tissue injury and antigenic challenge. Serial changes in the plasma concentrations of these two peptides were measured in 12 patients undergoing heart transplantation. Tissue concentrations of IL-6 in atrial samples from both donor and recipient hearts were also compared. Plasma IL-6 concentration remained stable prior to cardiopulmonary bypass (CPB), initially decreased with the onset of CPB, and then increased significantly over control values at the end of CPB (180 +/- 40 v 53 +/- 60 pg/mL). Plasma IL-6 remained elevated for at least 60 minutes after CPB, and then it returned to control values by 24 hours postoperatively (67 +/- 9 pg/mL). Examination of IL-6 changes after CPB in 10 additional patients undergoing nontransplant cardiac surgery with CPB revealed a similar elevation in IL-6 at 60 minutes after CPB (290 +/- 76 pg/mL). However, IL-6 in the nontransplant group remained significantly elevated at 24 hours (138 +/- 42 pg/mL). These combined results suggest that CPB causes a marked increase in IL-6, and that implantation of a new heart in transplant patients does not augment this increase. The return of IL-6 to control values by 24 hours in the patients who have had transplants suggests that immunosuppression has an appreciable effect on IL-6 at this time. In contrast to IL-6, plasma alpha MSH never increased above control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Spinal anesthesia in severe preeclampsia: a historical analysis of a reappraisal

Abstract Spinal anesthesia has recently been reported acceptable in women with severe preeclampsia. For example, taken together, a randomized study and a large retrospective review, comparing epidural and spinal for Cesarean, confirmed average reductions in MAP were mild (15–25%) for both epidural and spinal. Only moderate fluid loads administered without iatrogenic pulmonary edema, and total ephedrine dose was similar in each study without severe pressor response to a small IV bolus. In the past, the recommendation to avoid spinal was based on physiological changes leading to these concerns centered on fear of severe hypotension induced by sympathetic blockade, extreme sensitivity to pressors, and maternal hypovolemia of a variety of causes. Rapid infusion of large volumes of crystalloid or colloid given to correct severe hypotension has been implicated as a cause of pulmonary edema. In the early 1980s, a landmark comparative study of anesthesia for Cesarean by Hodgkinson showed the stable hemodynamics of epidural in contrast to the severe pressor responses with general. In the 1990s, reappraisal of spinal has occurred with advances in technology. Spinal has become popular and found to be cost-effective. In addition, a nationwide study of anesthesia-related maternal mortality identified significantly increased risk with general anesthesia, as compared to spinal and epidural.

M.T. Pepper Jenkins introduces Ringer's lactate to treat shock

Abstract M.T. Pepper Jenkins was one of the team that introduced balanced salt solutions (in those days, Ringers Lactate) to the resuscitation of traumatic shock. The revolutionary proposal is one of the most important innovations in the modern care of the surgical patient. Before 1950, surgeons and physiologists felt that salt solutions were contraindicated in surgical patients because they did not excrete a sodium load. Anesthetized patients were given small amounts of D5W, and if blood loss was excessive, they were given transfusions of whole blood. The turning point came in 1950 when Jenkins reported a series of critical patients in hemorrhagic shock, who received D5W and whole blood for resuscitation. They developed high hematocrits, stiff lungs and pulmonary failure, called “congestive atelectasis.” Jenkins theorized that congestive atelectasis could be prevented if Ringers Lactate was given with the blood. Over the next 30 years, Shires demonstrated the deficit of extracellular fluid, which occurs in hemorrhagic shock in dogs and humans, and the acute sequestered edema space that results from trauma. This work established the efficacy for the use of balanced salt solutions in shock. Salt solutions were not contraindicated, rather they are indicated and, in fact, life saving. Salt solutions are now used all over the world for the treatment of shock and have saved millions of lives. Our understanding of surgical fluid therapy has changed forever; and Jenkins could be compared to Copernicus who suggested that the earth and other planets rotate around the sun, changing the way we think about the universe.