Akira Kitamura

Patients with Diabetic Neuropathy Are at Risk of a Greater Intraoperative Reduction in Core Temperature

Background Core hypothermia develops after the induction of general anesthesia, but intraoperative vasoconstriction usually prevents its progression. However, diabetes mellitus is often associated with autonomic neuropathy, which leads to abnormal peripheral neurovascular function. Accordingly, we tested the hypothesis that diabetic patients experience a greater reduction in core temperature during general anesthesia than nondiabetic patients. Methods We studied 36 nondiabetic patients (control group) and 27 diabetic patients (diabetic group) undergoing elective abdominal surgery. Both groups were divided into young (< 60 yr) and older age (≥ 60 yr) groups. Standard noninvasive autonomic tests (heart rate variation at deep periodical breathing, Valsalva maneuver, and head-up tilt) were carried out for each patient. The relation between the results of these tests of autonomic function and the tympanic membrane temperature during general anesthesia was assessed in relation to peripheral vasoconstriction. Results Thirteen patients in the diabetic group showed abnormal responses to two or more of the basal autonomic function tests (patients with autonomic dysfunction). Changes in core temperature among the groups were similar at 90 min after the induction of anesthesia. However, the core temperature of the diabetic patients with autonomic dysfunction was lower from 120 min (35.1°C) onward compared with the young or older nondiabetic patients and the diabetic patients with normal autonomic function. Peripheral vasoconstriction, evaluated using the forearm–fingertip skin surface temperature gradient, was delayed in patients with autonomic dysfunction compared with the others. Conclusions The current results indicate that diabetic autonomic neuropathy is associated with more severe intraoperative hypothermia. We postulate that diabetic patients become more hypothermic because their peripheral neuropathy delays the onset of thermoregulatory vasoconstriction and reduces its efficacy once triggered. These patients may therefore fail to develop a normal core temperature plateau.

Efficacy of an ultrashort-acting beta-adrenoceptor blocker (ONO-1101) in attenuating cardiovascular responses to endotracheal intubation

AbstractObjective: To investigate the clinical effectiveness and safety of ONO-1101, a new ultrashort-acting (half-life 3–4 min), cardioselective β-adrenoceptor blocker in attenuating the cardiovascular responses to endotracheal intubation in a dose-finding open study.nn Methods: Laryngoscopy and tracheal intubation were performed after induction of anaesthesia with thiamylal, followed by administration of succinylcholine, and saline or ONO-1101 0.1, 0.25 or 0.5 mgu200a·u200akg−1, in 53 patients. Heart rate and blood pressure were continuously recorded beginning prior to administration until 5 min after administration of the drug, and the rate-pressure product was calculated.nn Results: ONO-1101 was found to significantly blunt the increase in heart rate throughout the study. Administration of ONO-1101 0.25 or 0.5 mgu200a·u200akg−1 decreased the incidence of tachycardia. However, these doses were not sufficient to suppress the increase in systolic blood pressure, although the maximal value in the ONO-1101 0.5 mgu200a·u200akg−1 group was reduced. Rate-pressure product increased significantly after intubation in all groups, but the increase was suppressed in the ONO-1101 0.25 and 0.5 mgu200a·u200akg−1 groups as compared with the saline group. Bradycardia was not observed in any patient, although hypotension might be caused by administration of ONO-1101 0.5 mgu200a·u200akg−1.nn Conclusion: ONO-1101, especially at a dose of 0.25␣mgu200a·u200akg−1, due to its β-adrenoceptor blockade and ultrashort action, was shown to be effective and well tolerated by patients in this study, when used to attenuate the cardiovascular responses to laryngoscopy and endotracheal intubation.

Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction.

Objective:To examine the association between decreased release of proinflammatory cytokines in response to urinary trypsin inhibitor pretreatment and decreased myocardial and lung injury after cardiopulmonary bypass. Design:A prospective, randomized, double-blind study. Setting:University hospital. Subjects:Thirty patients on cardiopulmonary bypass undergoing coronary artery bypass grafting. Interventions:Patients received 5000 units/kg intravenous urinary trypsin inhibitor (n = 15) or 0.9% saline (control, n = 15) immediately before aortic cannulation for cardiopulmonary bypass. Measurement and Main Results:Neutrophil elastase, tumor necrosis factor-&agr;, interleukin-6, and interleukin-8 were measured after intubation (T1), immediately before aortic cannulation (T2), after separation from cardiopulmonary bypass (T3), at the end of surgery (T4), and on postoperative days 1 (T5), 3 (T6), and 5 (T7). Simultaneous hematocrit values were obtained at all sample times. Isoenzyme of creatine kinase with muscle and brain subunits, troponin-T, and myosin light chain I were also measured. Various hemodynamic and pulmonary data were obtained perioperatively. Levels of neutrophil elastase and cytokines were corrected for hemodilution. Interleukin-6 and interleukin-8 levels were lower at T3 and T4 in the urinary trypsin inhibitor group than in the control group. Stroke volume index was significantly decreased in the control group at T3, and statistical difference was found between groups at T3 (p < .01). Respiratory index and intrapulmonary shunt were significantly higher in the control group than in the urinary trypsin inhibitor group at T3. Changes in respiratory index and intrapulmonary shunt correlated with interleukin-8 levels at T3 (r2 = .52, p < 00001; r2 = .37, p < 0001, respectively) and T4 (r2 = .44, p < .001; r2 = .24, p < .05, respectively). Neutrophil elastase levels and cardiac marker responses to coronary artery bypass grafting surgery were similar in both groups. Conclusions:Prepump administration of urinary trypsin inhibitor attenuates the elevation of interleukin-6 and interleukin-8 release immediately after cardiopulmonary bypass.

Epiduroscopic changes in patients undergoing single and repeated epidural injections.

Using a superfine fiberscope with an outer diameter of 0.75 mm, the effect of repeated injections through a single epidural catheter on the epidural space was examined in 18 patients. The subjects were divided into a control group of 10 patients who had not previously received epidural anesthesia (EA) and an EA group of 8 patients who had received repeated EA with 4-6 mL 0.25% bupivacaine through an epidural catheter, two to three times per day for 7-14 days. The epidural space was observed through a fiberscope passed through a 17-gauge Tuohy needle. The epidural space was occupied by large masses of fat, and the blood vessels and connective tissue were confirmed. Adverse reactions in the epidural tissue, such as hemorrhage or congestion with engorgement, were observed in four patients in the EA group. Five patients in the EA group experienced pain when the fiberscope was inserted into the epidural space. These investigations show that continuous EA might be followed by a high incidence of nonspecific epidural changes. Superfine fiberscope may be useful in the detection or diagnosis of local epidural reaction.

Systemic ATP infusion improves spontaneous pain and tactile allodynia, but not tactile hypesthesia, in patients with postherpetic neuralgia.

PurposeActivation of purinoceptors may improve neuropathic pain. Accordingly, the effects of systemic ATP infusion were assessed in patients with postherpetic neuralgia (PHN).MethodsEight patients with PHN lasting over 3 months were enrolled. Initially, patients received the vehicle (20% dextrose) or ATP (at a dose of 1u2009mg·kg−1 in 20% dextrose) infused intravenously for 60u2009min on two separate occasions in a single-blinded manner. The levels of spontaneous continuous pain, paroxysmal pain, and tactile allodynia were assessed by a visual analogue scale (VAS), and tactile hypesthesia was assessed by Semmes-Weinstein monofilament before and after infusion. Subsequently, the eight patients received an ATP infusion (1u2009mg·kg−1 in 20% dextrose) once a week for 5–12 weeks in an open-label manner, and changes in the above parameters were assessed.ResultsIn the initial study, VAS for spontaneous continuous pain and tactile allodynia decreased significantly with ATP infusion but not with placebo infusion. After repeated ATP infusions for 5–12 weeks, the median VAS for spontaneous continuous pain, paroxysmal pain, and tactile allodynia decreased significantly from 32.1 to 13.0, from 46.9 to 17.5, and from 49.5 to 15.6 respectively. However tactile hypesthesia did not improve significantly.ConclusionThis study demonstrated that repetitive intravenous ATP infusion could improve spontaneous continuous pain and paroxysmal pain, as well as improving tactile allodynia, but did not influence tactile hypesthesia.

Addition of epinephrine to intrathecal tetracaine augments depression of the bispectral index during intraoperative propofol sedation.

PurposeEpinephrine added to local anesthetic agents for spinal anesthesia is frequently used to prolong the duration of anesthesia. Epinephrine stimulates the Α-adrenoceptor, and it is known that the Α2-adrenoceptor agonists have a central inhibitory effect. We investigated the effect of intrathecal epinephrine during propofol sedation with spinal anesthesia, using a bispectral index (BIS) monitor.MethodsTwenty adult patients, scheduled for spinal anesthesia, were allocated to the control group (n = 10) or epinephrine group (n = 10). Patients in the control group received 14u2009mg of tetracaine, whereas the epinephrine group received 14u2009mg of tetracaine and 0.2u2009mg of epinephrine. Immediately after the pinprick test, propofol was administered at 0.5u2009mg·kg−1 by infusion for the initial dose, then continuously at 2u2009mg·kg−1·h−1 in both groups. BIS scores were recorded before subarachnoid block, and then every 5u2009min for 90u2009min after subarachnoid block.ResultsThere were significant differences in the BIS score between the two groups at 45–55u2009min and at 60–70u2009min after subarachnoid block.ConclusionIntrathecal epinephrine augments the sedative effect of propofol during spinal anesthesia.

Corticosteroid effect on down regulation in beta adrenergic receptors

Prolonged exposure to betaadrenergic agonists leads to loss of hemodynamic effectiveness. The mechanism of this desensitization is apparently a result of both a decrease in the number of beta-adrenergic receptors and an uncoupling of the receptors from adenyl cyclase. These changes occur with surprising rapidity. Unverferth et al., for example, demonstrated the development of tolerance to dobutamine after a 72h infusion. This finding has stimulated the discussion of the relative role of inotropic support, and led to interest in the combination of classes of agents. Lefkowitz and co-workers reported experiments that beta-adrenergic receptors are transcriptionally regulated by glucocorticoids in vitro, They proved that the rate of beta-adrenergic receptor gene transcription increased 3.1 fold in the glucocorticoid treated cells. Davies et al. reported that corticosteroid increased beta-adrenergic receptor in number in circulating polymorphonuclear leucocytes in normal human, Ogawa et al. confirmed this phenomenon in the clinical situation: they

Circulatory and metabolic changes in the brain during induced hypotension--comparison among trimetaphan, glycerin trinitrate and prostaglandin E1.

Induced hypotension was carried out using trimetaphan (TMP), glycerin trinitrate (GTN) and prostaglandin E1 (PGE1) in 45 patients received elective abdominal surgery under anesthesia with enflurane in N2O/O2 in order to evaluate and compare the effects of these three agents on cerebral circulation and metabolism. Upon reduction of mean arterial blood pressure to 60–65 mmHg, cerebral blood flow decreased in the TMP and GTN groups but increased in the PGE1 group. The changes were quite proportional to those in cardiac index in the three groups. Cerebral oxygen consumption decreased only in the TMP group. Changes in cerebrospinal fluid pressure were not in parallel with those in cerebral blood flow. The former decreased slightly in the TMP group but increased in the GTN and PGE1 groups. These results offered a great caution for induction of artificial hypotension using these agents.

Halothane modulates NMDA and non-NMDA excitatory synaptic transmission in rat cortical neurons.

PurposeAlthough general anesthetics may decrease neuronal excitation, their detailed effects on spontaneous excitatory postsynaptic currents (EPSCs) remain controversial. We investigated and compared the effects of halothane on N-methyl-d-asparate (NMDA) and non-NMDA receptor-mediated postsynaptic currents.MethodsSpontaneous synaptic currents were recorded by the patch clamp technique in cultured rat cortical neurons. They were isolated by specific pharmacological blocking agents and their electrophysiologic properties were examined.ResultsThe frequency of NMDA EPSCs was preferentially decreased as compared with that of non-NMDA EPSCs at halothane 1.2u2009mM. The total net charge of EPSCs mediated by NMDA and non-NMDA receptors was depressed to 56% ± 6% (mean ± SD) and 71% ± 7% of control by halothane 0.6u2009mM, and to 11% ± 9% and 59% ± 11% of control by halothane 1.2u2009mM, respectively.ConclusionThese results show that halothane causes decrease of excitatory synaptic activity, with NMDA EPSCs being more sensitive than non-NMDA EPSCs.