Hiroya Wakamatsu

The Effects of Moderate Hypothermia and Intrathecal Tetracaine on Glutamate Concentrations of Intrathecal Dialysate and Neurologic and Histopathologic Outcome in Transient Spinal Cord Ischemia in Rabbits

UNLABELLED The aim of the present study was to compare the effects of intrathecal tetracaine (a sodium channel blocker) with those of moderate hypothermia on glutamate concentrations of intrathecal dialysate, hindlimb motor functions, and histopathology in spinal cord ischemia. New Zealand White rabbits implanted with an intrathecal dialysis probe were assigned to one of the three groups (seven in each): control (temperature 38 degrees C), tetracaine (tetracaine 0.5%, 0.6 mL, given intrathecally 30 min before ischemia, 38 degrees C), or moderate hypothermia (32 degrees C). Spinal cord ischemia (20 min) was produced by occlusion of the abdominal aorta during isoflurane (1%) anesthesia. Glutamate concentrations significantly increased during ischemia in all groups, but the levels in the moderate hypothermia group were significantly lower than those in the control and tetracaine groups. Neurologic status (24 and 48 h after reperfusion) and histopathology (48 h) in the moderate hypothermia group were significantly better than in the other two groups. There were no significant differences between the tetracaine and control groups in either glutamate concentrations, neurologic status, or histopathology. We conclude that intrathecal tetracaine does not provide any protection against ischemic spinal cord injury, whereas moderate hypothermia does. IMPLICATIONS Sodium channel blockers, including local anesthetics, have been shown to reduce glutamate release in brain ischemia and have a neuroprotective effect. However, in the present study, intrathecal tetracaine did not attenuate either glutamate release or the neurologic or histopathologic outcome in spinal cord ischemia, whereas moderate hypothermia did.

The effects of N(G)-nitro-L-arginine-methyl ester on neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits.

UNLABELLED Little is known about the role of nitric oxide in the pathophysiology of spinal cord ischemia. We evaluated the effects of nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine-methyl ester (L-NAME) in rabbits whose abdominal aorta was occluded for 20 min (Experiment 1) or 25 min (Experiment 2). In Experiment 1, the L-NAME group (n = 6) received 3 mg/kg i.v. L-NAME, followed by an i.v. infusion of 3 mg x kg(-1). h(-1) until 6 h after reperfusion. Ischemia was induced 20 min after the start of L-NAME. The phenylephrine group (n = 6) received phenylephrine to maintain comparable blood pressure. The control group (n = 6) received saline. In Experiment 2, L-NAME (3 mg/kg i.v. L-NAME, followed by an i.v. infusion of 3 mg x kg(-1). h(-1) until 6 h after reperfusion) and phenylephrine groups (n = 6 each) were studied. Ischemia was induced 100 min after the start of L-NAME. Forty-eight hours after reperfusion, hindlimb motor function and histopathology of the spinal cord were examined. In Experiment 1, L-NAME and phenylephrine both improved neurologic outcome, with higher intraischemic blood pressures than saline. In Experiment 2, L-NAME worsened the neurologic and histopathologic outcome compared with phenylephrine. Attenuation of damage by L-NAME in Experiment 1 may be attributable to an intraischemic blood pressure increase. The worse outcome with L-NAME in Experiment 2 suggests that NOS inhibition exacerbates ischemic spinal cord damage. IMPLICATIONS Nonselective inhibition of nitric oxide synthase activity has aggravating effects on the neurologic and histopathologic outcome after transient spinal cord ischemia.

Glutamate release and neuronal injury after intrathecal injection of local anesthetics

High concentrations of local anesthetics are neurotoxic, but the mechanism for this neurotoxicity is obscure. Here, we report increased concentrations of glutamate in the cerebrospinal fluid after intrathecal injections of high concentrations of tetracaine (a local anesthetic). The peak concentrations of glutamate after administration of 1%, 2%, and 4% tetracaine were 4-fold, 6-fold, and 10-fold higher than baseline values, respectively. Animals in the 1% group were all neurologically normal one week after tetracaine injection. In the group receiving 4%, no animal was able to hop and vacuolation of the white matter and/or central chromatolysis of the motor neurons were observed. Because high concentrations of glutamate are known to be neurotoxic, our results may provide some insight into the mechanisms for neurotoxicity of intrathecal local anesthetics.

The time course of acquisition of ischemic tolerance and induction of heat shock protein 70 after a brief period of ischemia in the spinal cord in rabbits.

We examined the time course of development of ischemic tolerance in the spinal cord and sought its mechanism exploring the expression of heat shock protein 70 (HSP70). Spinal cord ischemia was produced in rabbits by occlusion of the abdominal aorta. In Experiment 1, neurologic and histopathologic outcome was evaluated 48 h after prolonged ischemia (20 min) that was given 2 days, 4 days, or 7 days after a short period of ischemia (ischemic pretreatment) sufficient to abolish postsynaptic component of spinal cord evoked potentials. Control animals were given prolonged ischemia 4 days after sham operation. In Experiment 2, HSP70 expression in motor neurons after pretreatment without exposure to prolonged ischemia was examined by immunohistochemical staining. Ischemic pretreatment 4 days (but not 2 days or 7 days) before 20 min ischemia exhibited protective effects against spinal cord injury. In the cytoplasm, HSP70 immunoreactivity was mildly increased after 2, 4, and 7 days of ischemic pretreatment. However, the incidence of nuclear HSP70 immunoreactivity 2 days, 4 days, and 7 days after ischemic pretreatment was 2 of 6 animals, 4 of 6 animals, and 1 of 6 animals, respectively (none in the control group). These results suggest that ischemic tolerance is apparent 4 days after ischemic pretreatment and that HSP70 immunoreactivity in the nucleus may provide some insight into the mechanisms of ischemic tolerance in the spinal cord.

Perioperative management for placement of tracheobronchial stents.

Tracheobronchial stenting was performed under general anesthesia, with (six patients) or without (two patients) muscle relaxant, in eight patients suffering from carcinoma. All patients had presented preoperatively with dyspnea, exhibiting Hugh-Jones grade 4 or 5. Three patients had been mechanically ventilated before the procedure. The procedure was performed under general anesthesia with flexible bronchoscopic guidance. Stent placement was performed either through an orotracheal tube (four patients) or through a transtracheal tube (two patients) in those who had no upper tracheal stenosis, while it was performed through a laryngeal mask airway in two patients with upper tracheal stenosis. During the procedure, arterial hemoglobin oxygen saturation (SpO2) decreased in all patients, despite fraction of inspired oxygen (FIO2) being maintained at 1.0. Except for two patients, one of whom developed superior vena cava syndrome and one, tension pneumothorax after stent placement, there were no complications resulting from stent placement. Six patients were weaned from mechanical ventilation (0–24 days after the procedure). Two of the three patients who had been on mechanical ventilation preoperatively could not be weaned. Stent insertion is an effective treatment for tracheobronchial stenosis, but its indications in patients with malignancy who have been mechanically ventilated prior to stenting should further be evaluated.

Reliability and validity assessment of the Japanese version of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)

OBJECTIVE Delirium may lead to adverse outcomes in patients with serious conditions, but is often under-diagnosed due to inadequate screening. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is an established method for assessing delirium in the ICU. The validity and reliability of the Japanese version of the CAM-ICU has not, however, been verified, and we undertook this study to verify these parameters. RESEARCH METHODOLOGY CAM-ICU validity and reliability were assessed in two Japanese ICUs. Using the evaluation of the DMS-IV-TR in the psychiatrists group as the standard criteria for delirium diagnosis, we compared the evaluation of the Japanese version of the CAM-ICU between the research nurses group and the staff nurses group. RESULTS According to DSM-IV-TR criteria, the prevalence of delirium was 22.0%, and according to CAM-ICU delirium was found in 22.0% with Research Nurses and 19.5% with Staff Nurses. CAM-ICU sensitivity ratings were 83% and 78%, while their specificity ratings were 95% and 97%, respectively. The Kappa inter-rater reliability was good (κ=0.85), and Cronbachs alpha coefficient was 0.69 (95% CI: 0.57-0.79). Mean rating time for the CAM-ICU was 2.5-2.8 minutes for Research Nurses and Staff Nurses, respectively. CONCLUSION The Japanese version of the CAM-ICU has comparable validity and reliability as a delirium assessment tool in surgical patients in two Japanese ICUs. With training, CAM-ICU can be incorporated into daily clinical practice.

The effects of cyclosporin A and insulin on ischemic spinal cord injury in rabbits.

We examined the effects of cyclosporin A (CsA), a drug that inhibits mitochondrial permeability transition pore, and insulin on ischemic spinal cord damage in rabbits. We assigned rabbits to 5 groups (n = 6 in each); sham barrier-opened group (sham BO), barrier-opened group (BO), barrier-opened-CsA group (BO-CsA), barrier-opened-insulin group (BO-I), and barrier-opened-CsA-insulin group (BO-CsA-I). The blood-spinal cord barrier was opened to facilitate drug penetration by a mild injury to the lumber spinal cord on day 1. CsA (10 mg/kg per day IV) was administered on day 3 to day 5 (total 30 mg/kg). Insulin was administered 30 min before ischemia. In all groups, spinal cord ischemia was produced on day 5 by occluding the abdominal aorta for 13 min. Neurological and histopathological evaluations were performed 4 days after ischemia. In group BO-CsA, blood glucose concentrations were significantly larger compared with the other four groups, and no protection was observed. In contrast, hindlimb motor function in groups BO-I and Bo-CsA-I and histopathology in group BO-CsA-I were significantly better than in groups sham BO, BO, and BO-CsA. The results indicate that insulin protects against ischemic spinal cord injury, whereas the effect of CsA is, at best, minimal.

Fentanyl pretreatment attenuates the haemodynamic response to sudden inhalation of 5% isoflurane

High concentrations of inhaled isoflurane can increase heart rate and/or arterial pressure. The purpose of this study was to determine whether fentanyl has a prophylactic effect on the isoflurane-induced circulatory response in adult patients. Thirty patients due to undergo elective surgery were randomly allocated to one of three groups of ten patients. Prior to surgery, one group inhaled 2.5% isoflurane, another inhaled 5.0% isoflurane, and the third group inhaled 5.0% isoflurane and were given fentanyl 2 μg · kg−1 iv two minutes before induction of anaesthesia. Anaesthesia was induced with thiamylal followed by vecuronium. The lungs were ventilated with 100% oxygen and either 2.5% or 5.0% isoflurane via face mask. Ventilation was continued for five minutes. Heart rate (HR) and mean arterial pressure (MAP) were recorded at two minutes before induction of anaesthesia (baseline), immediately before the induction of anaesthesia, and at three and five minutes after induction, respectively. It was found that 5.0% isoflurane caused an increase in HR compared with baseline (P < 0.01) and with the 2.5% isoflurane (P < 0.05): 2.5% isoflurane did not elicit this response. An increase was also noted in MAP, compared with the 2.5% isoflurane (P < 0.01): 2.5% isoflurane did not elicit this increase. Fentanyl pretreatment attenuated the increases in HR and in MAP that occurred with 5.0% isoflurane (P < 0.01). These results suggest that fentanyl attenuates the enhancement of both HR and MAP from face mask inhalation of a high concentration of isoflurane.RésuméL’inhalation de fortes concentrations d’isoflurane peut augmenter la fréquence cardiaque et la pression artérielle. Cette étude a pour objectif de déterminer si le fentanyl protège le sujet adulte de ces réponses circulatoires induites par l’isoflurane. Trente patients programmés pour une chirurgie non urgente sont répartis au hasard en trois groupes égaux. Avant la chirurgie, un groupe inspire de l’isoflurane à 2,5%, le deuxième de l’isoflurane à 5%, et le troisième de l’isoflurane à 5% et reçoit du fentanyl 2 μg · kg−1 iv deux minutes avant l’induction de l’anesthésie. L’anesthésie est induite avec du thiamylal suivi de vécuronium au masque facial. Les poumons sont ventilés avec de l’oxygène à 100% associé à l’isoflurane 2,5% ou 5%. La ventilation est continuée pendant cinq minutes. La fréquence cardiaque (FC) et la pression artérielle moyenne (PAM) sont enregistrées deux minutes avant l’induction (mesure initiale), immédiatement avant l’induction de l’anesthésie et trois et cinq minutes après l’induction. Les résultats montrent que l’isoflurane à 5% produit une augmentation de FC comparativement à la mesure initiale (P < 0,01): mais que l’isoflurane à 2,5% ne provoque pas cette réponse (P < 0,05). Une augmentation de la MAP est aussi notée comparativement à l’isoflurane 2,5% (P < 0,01):l’isoflurane 2,5% ne provoque pas cette augmentation. Le prétraitement au fentanyl diminue l’augmentation de la FC et de la MAP qui survient avec l’isoflurane 5% (P < 0,01). Ces résultats suggèrent que le fentanyl atténue l’augmentation à la fois de la FC et de la MAP pendant l’administration au masque de concentrations élevées d’isoflurane.