Takaaki Kitano

Respiratory mechanics and arterial blood gases during and after laparoscopic cholecystectomy

PurposeThe purpose of this study was to assess the effects of increased intra-abdominal pressure due to CO2 insufflation on the mechanical characteristics of the respiratory system and arterial blood gases during and after laparoscopic cholecystectomy.MethodsRespiratory mechanics and arterial blood gases were examined in 12 patients undergoing laparoscopic cholecystectomy with CO2 insufflation. Respiratory mechanics were continuously monitored with in-line spirometry. In the recovery room, PaCO2 was measured in this group at 30 min and compared with PaCO2s in 23 patients who had undergone open cholecystectomy retrospectively, to evaluate the effects of insufflation on CO2 elimination.ResultsMinute ventilation was decreased by about 500 ml·min−1 during abdominal insufflation. Dynamic lung compliance decreased from 49.6 ± 4.7 to 30.7 ±2.3 (mean ± SEM) ml·cmH2O−1 with abdominal insufflation (P < 0.005), and returned to 45.1 ±3.1 after the release of pneumoperitoneum. Peak inspiratory pressure increased from 15.9 ± 0.9 to 18.9 ± 1.0 cmH2O with abdominal insufflation (P < 0.05). Arterial blood gas determinations indicated a decrease in arterial pH, with CO2 retention during insufflation and in the recovery room (P < 0.05). PaCO2 of the laparoscopic patients was higher than that of the open patients in the recovery room.ConclusionThe results indicate that respiratory acidosis was caused during CO2 insufflation for laparoscopic cholecystectomy, that was due to (1) decreased compliance, (2) increased CO2 load and (3) insufficient ventilation. Accumulated CO2 during laparoscopic cholecystectomy increased PaCO2 level in the recovery room.RésuméObjectifEvaluer les effets de l’augmentation de pression intraabdominale provoquée par l’insufflation de CO2 sur les caractéristiques du système respiratoire et des gaz du sang artériel pendant et après la cholécystectomie laparoscopique.MéthodeLa mécanique respiratoire et les gaz du sang artériels ont été étudiés chez 123 patients soumis à une cholé-cystectomie laparoscopique avec insufflation de CO2. La mécanique respiratore a été monitorée en continu par spirométrie. A la salle de réveil, la PaCO2 a été mésurée à la 30e min de l’admission et comparée rétrospectivement à la PaCO2 de 23 patients qui avaient subi une cholécystectomie ouverte, dans le but d’évaluer les effets de l’insufflation sur l’élimination du CO2.RésultatsLa ventilation minute a diminué d’environ 500 ml·min−1 pendant l’insufflation abdominale. La compliance dynamique pulmonaire diminuait de 49,6 ± 4,7 à 30,7 ± 2,3 (moyenne ± SEM) ml·cmH2O−1 avec l’insufflation (P < 0,005) et revenait à 45,1 ± 3,1 après le relâchement du pneumopéritoine. L’analyse des gaz artériels a révélé une diminution du pH artériel avec rétention de CO2 pendant l’insufflation et à la salle de réveil (P < 0,005). La PaCO2 des patients opérés sous laparoscopie était plus élevée que celle des patients opérés par chirurgie ouverte.ConclusionCes résultats indiquent que l’insufflation de CO2 pour la cholécystectomie laparoscopique provoque de l’acidose respiratoire causée 1) par la baisse de la compliance, 2) l’augmentation du volume de CO2 et 3) l’insuffisance ventilatoire. L’accumulation du CO2 pendant la cholécystectomie laparoscopique augmente la PaCO2 à la salle de réveil.

Glucose intolerance during prolonged sevoflurane anaesthesia.

PurposeThe effects of prolonged sevoflurane anaesthesia on insulin sensitivity were investigated by two successive intravenous glucose tolerance tests (IVGTT) in eight patients who underwent prolonged surgery.MethodsThe first IVGTT was administered (25 g glucose as 20% dextrose in water iv) over two minutes 35 min after initiation of surgery. Arterial blood samples were obtained at 0, 5, 10, 30, 60, and 120 min after glucose administration for blood glucose and plasma insulin determination. A second IVGTT was performed six hours following the initiation of surgery.ResultsThe disappearance rate of glucose (k-value) for the first IVGTT was 0.887 ± 0.436 (mean ± SD) % · min−1, and 0.784 ± 0.289 for the second IVGTT. Both k-values are lower than the normal value. The maximum insulin response to glucose (ΔIRI · ΔBS−1) of the second IVGTT was lower than the first IVGTT (0.124 ± 0.092 vs 0.071 ± 0.056, P < 0.05). The total insulin output of the first IVGTT was higher than the second IVGTT (1,161 ± 830 vs 568 ± 389 μU · min · ml−1, P < 0.05).ConclusionGlucose intolerance is enhanced by diminished insulin output in response to blood glucose elevation during prolonged anaesthesia and surgery.RésuméObjectifLa réalisation d’épreuves d’hyperglycémie provoquée (HGP) chez huit patients soumis à une chirurgie de longue durée visait à étudier les effets de l’administration prolongée de sévoflurane sur la sensibilité à l’insuline.MéthodesLa première épreuve d’HGP (25 g de glucose administrés iv sous la forme d’une solution glucosée 20% dans l’eau) a été effectuée en deux minutes, 35 min après le début de la chirurgie. Des échantillons de sang artériel ont été prélevés 0, 5, 10, 30, 60 et 120 min après l’administration de glucose pour déterminer la glycémie et l’insulinémie. Une deuxième HGP a été réalisée six heures après le début de la chirurgie.RésultatsLes résultats de la première HGP ont montré que la vitesse de disparition du glucose (valeur k) était de 0,887 ± 0,436 (moyenne ± ET)% · min−1, alors que la deuxième épreuve titrait 0,784 ± 0,289. La réponse insulinique maximale au glucose (ΔIRI · ΔBS−1) de la deuxième HGP était inférieure à celle de la première (0,124 ± 0,92 vs 0,071 ± 0,056, P < 0,05). Avec la première HGP, le débit total de l’insuline était plus élevé qu’avec la deuxième (1,161 ± 830 vs 568 ± 389 μU · min · ml−1, P < 0.05).ConclusionL’intolérance au glucose est amplifiée par une baisse de la production d’insuline en réponse à l’élévation de la glycémie pendant l’anesthésie et la chirurgie prolongées.

Lactate utilization as an energy substrate in ischemic preconditioned rat brain slices

We examined the utilization of lactate as an energy substrate in ischemic preconditioned slices obtained from the rat brain left hemisphere, of which the contralateral middle cerebral artery was occluded 48 h before the slice preparation. The levels of high-energy phosphates in the brain slices were measured using 31P NMR with a time resolution of 4 min at 25 degrees C. When iodoacetic acid-pretreated brain slices were further treated with fluorocitrate, a glial toxin, for 2 h (neuron-rich slices), the recovery of the phosphocreatine (PCr) level in artificial cerebrospinal fluid (ACSF) containing lactate after high-K+ stimulation was completely abolished in intact slices, whereas the PCr level in ischemic preconditioned slices well recovered in otherwise similar conditions. These results indicated that neurons, when preconditioned with ischemia, acquire the ability to utilize lactate as an energy substrate. In parallel experiments, we recorded population excitatory postsynaptic potentials and spikes from granule cells in hippocampal slices. Population spikes of intact slices in ACSF containing lactate were completely abolished in 30 min, but those of the ischemic preconditioned slices were maintained well over 50%. These results show that ischemic preconditioning may induce certain systematic changes in neurons, such as the expression of lactate transporters and/or the activation of lactate dehydrogenase.

Monocarboxylates and glucose utilization as energy substrates in rat brain slices under selective glial poisoning – a 31P NMR study

We have investigated effects of various energy substrates including glucose, lactate and pyruvate on the recovery of the high energy phosphate levels after high-K+ stimulation in rat brain slices by using 31P NMR. It was found that lactate, pyruvate and glucose almost equally supported the recovery of phosphocreatine (PCr) levels after high-K+ stimulation (60 mM, 8 min) in artificial cerebrospinal fluid (ACSF). In iodoacetic acid (IAA) and fluorocitrate (FC)-pretreated slices, whereas glucose was unable to be utilized, the recovery of the PCr level after high-K+ stimulation in ACSF containing lactate was completely abolished, the recovery of the PCr in ACSF containing pyruvate was unaffected. These results indicate that neurons themselves can utilize pyruvate as an exogenous energy substrate, but not lactate, without glial support. In intact brain, glucose may be metabolized to pyruvate in glial cells and then transported to neurons as an energy substrate. These suggest an astrocyte-neuron pyruvate shuttle mechanism of the brain energy metabolism in vivo.We also investigated the effect of ischemic-preconditioning in FC-pretreated slices, which showed that the PCr levels recovered substantially in ACSF containing lactate after high-K+ stimulation. This indicates that after the preconditioning, such as ischemia, neurons themselves acquired the ability to utilize lactate as an energy substrate.

Flecainide reverses neuropathic pain and suppresses ectopic nerve discharge in rats.

We investigated effects of flecainide, a Class IC sodium channel blocker, in the rat chronic constrictive injury (CCI) and ectopic nerve discharge models. In the behavioral evaluation, 2, 6, and 12 mg/kg flecainide were intravenously given to the CCI model, and a dose-dependent analgesic effect was shown on both thermal hyperalgesia and tactile allodynia. In the electrophysiological evaluation using the ectopic nerve discharge model produced by saphenous neurectomy, i.v. administration of 2, 6, and 12 mg/kg flecainide suppressed spontaneous discharge at the peripheral nerve level in a dose-dependent fashion as with the behavioral evaluation, but flecainide did not affect nerve conduction at the dose of 12 mg/kg.

Olprinone improves diaphragmatic contractility and fatigability during abdominal sepsis in a rat model.

Background:  Respiratory failure with diaphragmatic fatigability is common in patients suffering sepsis or septic shock. However, the development and progress of diaphragmatic fatigability remains poorly understood, and no method has been established to treat fatigability. In this study, we hypothesize that neutrophil activation contributes to the development of diaphragmatic fatigability. We also sought to investigate whether a phosphodiesterase inhibitor, olprinone, improves diaphragmatic fatigability associated with abdominal sepsis and inhibits an increase in myeloperoxidase activity in diaphragmatic muscle.

Neutrophilia and granulocyte colony-stimulating factor levels after cardiopulmonary bypass.

Purpose: The precise mechanism of neutrophilia after cardiac surgery is unknown. Granulocyte colony stimulating factor (G-CSF) can increase the number of leukocytes. The purpose of this study was to evaluate the relationship between serum G-CSF levels and peripheral blood leukocyte counts after cardiac surgery.Methods: We prospectively studied 10 patients undergoing cardiac surgery (coronary artery bypass grafting) using cardiopulmonary bypass (CPB). Plasma G-CSF levels and neutrophil count were measured before induction of anaesthesia, at the end of surgery, and on the first postoperative day. These changes were compared with those in patients undergoing non-cardiac major surgery (control group).Results: At the end of surgery, G-CSF levels increased (P<0.01) in both groups, but were higher in the control than in the cardiac group (3,250±690vs 194±29.5 pg·ml−1, respectively, mean±SEM,P<0.01). On the first postoperative day, G-CSF levels were still high in both groups, and were still higher in the control (710 ±179vs 122±19.9, respectively,P<0.01). However, neutrophilia was greater in the cardiac group than in the control. G-CSF response correlated positively with neutrophilia in the control group (r=0.656,P<0.05) but not in the cardiac group.Conclusions: Our results indicate that changes in leukocyte count following cardiac surgery are unique to patients undergoing CPB. G-CSF plays an important role as the mediator of neutrophilia after non-cardiac surgery, but not after cardiac surgery with CPB.RésuméObjectif: Le mécanisme précis de la polynucléose neutrophile qui survient après une intervention en cardiochirurgie est inconnu. Le facteur stimulant la formation de colonies de granulocytes (FSC-G) peut augmenter le nombre de leucocytes. L’objectif de la présente étude était d’évaluer la relation entre les niveaux sériques de FSC-G et la numération leucocytaire du sang périphérique à la suite d’une intervention cardiaque.Méthode: Nous avons mené une étude prospective auprès de 10 patients qui ont subi un pontage aorto-coronarien sous circulation extracorporelle (CEC). Les niveaux plasmatiques de FSC-G et la numération des neutrophiles ont été mesurés avant l’induction de l’anesthésie, à la fin de l’opération et au premier jour postopératoire. Les changements ont été comparés avec ceux qu’on a observés chez des patients qui ont subi une intervention importante, non cardiaque (groupe témoin).Résultats: À la fin de l’opération, les niveaux de FSC-G ont augmenté (P<0,01) dans les deux groupes, mais ont été plus élevés dans le groupe témoin que dans le groupe de cardiochirurgie (3,250±690vs 194±29,5 pg·ml−1, respectivement, moyenne±écart type,P<0,01). Au premier jour postopératoire, les niveaux de FSC-G étaient encore élevés dans les deux groupes et toujours plus hauts chez les témoins (710±179vs 122±19,9, respectivement,P<0,01). Toutefois, la polynucléose neutrophile était plus marquée dans le groupe de cardiochirurgie que dans le groupe témoin. La réponse du FSC-G était en corrélation avec la polynucléose neutrophile dans le groupe témoin (r=0,656,P<0,05) mais non dans l’autre groupe.Conclusion: Nos résultats indiquent que les changements de numération des leucocytes, à la suite d’une intervention cardiaque, sont uniques aux patients qui subissent une CEC. Le FSC-G joue un rôle important comme médiateur de la polynucléose neutrophile après une opération non cardiaque, mais pas après une intervention cardiaque sous CEC.

The Effects of Circulating Interleukin-8 and Adhesion Molecules on Pulmonary Dysfunction in Pediatric Orthotopic Liver Transplantation

We investigated the effects of circulating inflammatory cytokines and adhesion molecules induced by orthotopic liver transplantation (OLT) on pulmonary function. Although the plasma interleukin-8 (IL-8) levels increased gradually, peaking at the end of the operation, these increases were considered minimal. The baseline endothelial adhesion molecule (E-selectin) level was several times higher than the normal value, but after reperfusion of the new transplanted liver, the plasma E-selectin concentrations decreased to within the normal range and remained almost normal during the postoperative period. Similar changes were observed in the plasma levels of other types of adhesion molecules. Although PaO2/FIO2 showed a significant inversed correlation with the peak IL-8 concentration, after the exclusion of two patients, one of whom died and one of whom rejected the transplanted liver, no correlation was able to be found between the PaO2/FIO2 ratio and the maximum IL-8 concentration. Furthermore, there was no correlation between the adhesion moleclues and PaO2/FIO2. These results suggest that IL-8 exerts only a slight effect on respiratory function following successful pediatric liver transplantation, and that circulating adhesion molecules do not affect perioperative lung function.

Continuous monitoring of ventilatory mechanics during one-lung ventilation

Objective. The Ultima SV respiratory monitor can be used to monitor the intraoperative effects of the lateral decubitus position and one-lung ventilation on ventilatory mechanics.Methods. Eight patients with esophageal cancer who required one-lung ventilation for esophagectomy and reconstruction were enrolled in the study. We monitored pressure-volume or flow-rate-volume loops continuously throughout the operation. Respiratory parameters were evaluated closely during five conditions of ventilation: two-lung ventilation in the supine position, two-lung ventilation in the lateral decubitus position, dependent one-lung ventilation in the lateral decubitus position, nondependent one-lung ventilation in the lateral decubitus position, and dependent one-lung ventilation in the lateral decubitus position with the chest opened. Respiratory rate was controlled at 10 breaths/min, and tidal volume was kept constant (10 ml/kg) during surgery.Results. Peak inspiratory pressure increased to 29.0 ± 9.0 (mean ± SD) cm H2O in the dependent one-lung in the lateral decubitus position with the chest opened (p < 0.01). Dynamic compliance decreased to 29.4 ± 4.9 ml/cm H2O in the dependent one-lung in the lateral decubitus position with the chest opened (p < 0.01). The changing configuration of the loops also offered additional and instantaneous information during one-lung ventilation.Conclusions. One-lung ventilation caused several changes in the whole respiratory system (lung, thorax, and endotracheal tube). Continuous monitoring of flow-rate-volume or pressure-volume loops with in-line spirometry provided comprehensive information regarding parameters in one-lung ventilation.

The efficacy and safety of antithrombin and recombinant human thrombomodulin combination therapy in patients with severe sepsis and disseminated intravascular coagulation.

PURPOSE Recombinant human thrombomodulin (rhTM) is often used concomitantly with antithrombin (AT) to treat disseminated intravascular coagulation (DIC). This observational study aimed to investigate the efficacy and safety of AT+rhTM combination therapy. MATERIALS AND METHODS One hundred twenty-nine patients with severe sepsis and DIC participated in this study. Of these, 78 patients were treated with AT+rhTM (AT+rhTM group) and 51 patients were treated with AT alone (AT group). We compared coagulation and inflammation markers, Sequential Organ Failure Assessment score, and DIC score at day 0 (baseline) and day 7 between the 2 groups. Bleeding events and 28-day mortality were also compared. RESULTS Platelet counts and D-dimer levels at day 7 significantly improved in the AT+rhTM group compared with the AT group, and 28-day mortality was significantly lower in the AT+rhTM group than in the AT group (AT+rhTM: 15.4% vs AT: 29.4%). During the study period, the incidence of bleeding complications was similar in both groups (AT+rhTM: 6.4% vs AT: 7.8%). CONCLUSIONS Compared with AT monotherapy, combination therapy with AT and rhTM may be more effective in improving platelet counts and D-dimer levels, as well as reducing mortality, in patients with severe sepsis-associated DIC.