Keiji Enzan

Use of the bispectral index during the early postresuscitative phase after out-of-hospital cardiac arrest

Non-invasive and real-time measures of neurological status after cardiac arrest are needed to be able to make an early determination of the postresuscitative outcome. We investigated whether the bispectral index (BIS) predicts the postresuscitative outcome in 10 patients with out-of-hospital cardiac arrest. We measured the BIS after return of spontaneous circulation (ROSC) in the emergency room and on admission to the intensive care unit (ICU). We determined the Glasgow Coma Scale (GCS) on admission to the emergency room and the ICU and the Glasgow Outcome Scale (GOS) on discharge from the ICU. The BIS increased after about 30 min of ROSC or reached a plateau in patients rated as achieving a good recovery or moderate disability, but it did not increase to >80 in patients rated as being in a permanent vegetative state/dead. The GCS on admission to the ICU was the same as that on admission to the emergency room. The BIS values were significantly lower in the nonsurviving group than in the surviving group. There was a positive correlation between the BIS on admission to the ICU and the GOS on discharge from the ICU. The BIS can thus be used to predict the postresuscitative outcome of patients with out-of-hospital cardiac arrest.

Estimating the effect of bystander-initiated cardiopulmonary resuscitation in Japan

Low incidence of bystander-initiated cardiopulmonary resuscitation (CPR) is allegedly responsible for poor survival from out-of-hospital cardiac arrest (OHCA) in Japan. This study was conducted to determine significant predictors for survival after collapse-witnessed OHCA of presumed cardiac etiology to investigate the impact of bystander-initiated CPR. Logistic regression analysis of OHCA of presumed cardiac etiology was performed on retrospective data sets from three Japanese suburban communities. All arrest incidents were witnessed and occurred prior to the arrival of EMS personnel. Outcome measure was survival to discharge. Initial electrocardiogram (ECG) rhythm (ventricular fibrillation (VF) or not), interval from collapse to CPR (within 5 min or not), and initial ECG rhythm/collapse-to-CPR interval interaction were significantly associated with survival. Patient age (70 years or less/over 70 years), interval from collapse to EMS response, and bystander-initiated CPR were significantly associated with VF in an initial ECG. The effectiveness of bystander-initiated CPR for OHCA can be successfully predicted based on the interval from collapse to CPR and initial ECG rhythm. The increase in the proportion of bystander-initiated CPR from the present level of 20-50% would be expected to rescue another 1800 victims of OHCA per year in Japan.

Heparin-protamine complexes cause pulmonary hypertension in goats

Background Protamine reversal of heparin-induced anticoagulation causes thromboxane release followed by pulmonary vasoconstriction in sheep and pigs. The aim of this study was to determine whether heparin-protamine (H-P) complexes are causative agents of thromboxane release followed by pulmonary hypertension associated with protamine reversal of heparin.

Nitrous oxide administration during washout of sevoflurane improves postanesthetic agitation in children.

The use of sevoflurane in pediatric patients, which could enable a more rapid emergence and recovery, is complicated by a high incidence of postanesthetic agitation, probably due to residual sevoflurane during washout. The present study was designed to investigate whether administration of nitrous oxide (N2O) reduces sevoflurane concentration at awakening and suppresses postanesthetic agitation. The study enrolled 20 children classified as ASA physical status I. Anesthesia was induced with 5% sevoflurane and maintained with 2.5% end-tidal sevoflurane and N2O in oxygen. In the control group, sevoflurane and N2O were discontinued immediately after completion of surgery. In the N2O group, inspired N2O was replaced with oxygen after the bispectral index (BIS) had reached 80. The end-tidal concentrations of sevoflurane at awakening were significantly lower (P < 0.05) in the N2O group than in the control group. The BIS at awakening was higher (P < 0.01) in the N2O group than in the control group. The point scores of postanesthetic agitation were significantly lower (P < 0.01) in the N2O group than in the control group. Using N2O during washing out of sevoflurane may improve postanesthetic agitation at awakening in children.

Dibutyryl cAMP improves systemic vasoconstriction caused by endotoxin in dogs.

We studied whether dibutyryl cyclic adenosine monophosphate (DbcAMP), which freely penetrates into the cells, improves systemic vasoconstriction caused by endotoxin in dogs. Thirteen anesthetized dogs were randomized into three groups. The endotoxin (ETX) group (n = 5) received only Escherichia coli endotoxin (3 mg-kg-1, intravenously). The ETX + DbcAMP group (n = 5) received DbcAMP (6 mg-kg-1, intravenously) 30 min before the administration of endotoxin. The DbcAMP group received the same dose of DbcAMP 30 min after administration of saline. In the ETX group, systemic blood pressure and cardiac index significantly decreased, and systemic vascular resistance significantly increased, while in the ETX + DbcAMP group, increases in systemic and pulmonary vascular resistances after the administration of endotoxin were attenuated. DbcAMP did not cause hemodynamic changes in normal dogs. Plasma concentrations in thromboxane B2 in the ETX group were higher than in the ETX + DbcAMP group. Also, the change in plasma cyclic AMP concentrations showed a good logarithmic correlation with the change in plasma thromboxane B2 concentrations after the administration of endotoxin (r = .908, Log (ΔTxB2) = -.002*(ΔcAMP) + 3.786). We conclude that DbcAMP improves systemic vasoconstriction caused by endotoxin in dogs. The beneficial mechanism of DbcAMP on systemic vasoconstriction after the administration of endotoxin may be partially due to inhibition of thromboxane B2.

Systemic hypotensive response to protamine following chronic inhibition of nitric oxide synthase in rats

PurposeThe aims of the present studies were to determine whether the systemic hypotensive response to protamine was modified in rats pre-treated for two weeks with the nitric oxide synthase inhibitor, NG-nitro-L-argi-nine-methyl ester (L-NAME), and to evaluate the inhibitory effect of heparin on the systemic hypotensive response to protaminein vivo.MethodsMale rats were randomly assigned into four groups. Normal saline 12μl·day−1, D-NAME (an inactive enantiomer of L-NAME), 10 mg·kg−1·day−1, L-NAME, 1 or 10 mg·kg−1·day−1ip was administered for two weeks and the haemodynamic changes were measured after protamine administration. In another experiment, male rats were assigned to two groups. In one, the heparin group, protamine was administered after heparin had been administered and in the other, protamine group, protamine alone was administered.ResultsL-NAME inhibited the decrease in systemic arterial pressure after protamine administration (P < 0.05), but D-NAME had no effect. Also, heparin reduced the decrease in systemic arterial pressure after protamine (P < 0.05).ConclusionNitric oxide is mainly responsible for mediation of the systemic hypotensive response to protamine which is also reduced by heparin.RésuméObjectifL’objectif des présentes études était de déterminer si la réaction hypotensive généralisée à la protamine était modifiée chez les rats prétraités pendant deux semaines avec l’inhibiteur de l’oxyde nitrique synthase, NG-nitro-L-arginine-methyl ester (L-NAME), et d’évaluer l’effet inhibiteur de l’héparine sur la réaction hypotensive généralisée à la protamine,in vivo.MéthodeDes rats mâles ont été répartis au hasard en quatre groupes. Une solution salée de 12 μl·jour−1, DNAME (un énantiomère inactif de L-NAME), 10 mg·kg−1·jour−1, L-NAME, 1 ou 10 mg·kg−1·jour−1ip a été administré pendant deux semaines et les changements hémodynamiques ont été mesurés après l’administration de protamine. Lors d’une autre expérience, les rats ont été divisés en deux groupes. Dans l’un d’eux, le groupe héparine, l’administration de la protamine a suivi celle de l’héparine et, dans l’autre groupe, le groupe protamine, seule la protamine a été administrée.RésultatsL-NAME a empêché la baisse de tension artérielle générale après l’administration de la protamine (P < 0,05), mais D-NAME n’a pas eu d’effet. De même, l’héparine a réduit la baisse de la tension artérielle générale après l’administration de protamine (P < 0,05).ConclusionLoxyde nitrique est principalement responsable de la médiation de la réaction hypotensive généralisée à la protamine, laquelle est aussi réduite par l’héparine.

Platelet-activating factor is a key mediator of pulmonary vasoconstriction and bronchoconstriction after antigen challenge in the perfused sensitized rabbit lung

ABSTRACT Exposure of sensitized perfused rabbit lungs to human O-N type erythrocytes leads to pulmonary vasoconstriction and bronchoconstriction. To investigate whether platelet-activating factor (PAF) is a mediator of pulmonary vasoconstrictive and bronchoconstrictive responses after antigen challenge, we administered antigenic erythrocytes after the administration of PAF antagonist (.1 mg/kg; CV6209). Pulmonary arterial and airway pressures significantly increased after antigen challenge in the sensitized rabbit lungs, but not in the nonsensitized rabbit lungs. CV6209 significantly inhibited these pulmonary vasoconstrictive and bronchoconstrictive responses after antigen challenge. We concluded that PAF, at least in part, plays an important role in pulmonary vasoconstriction and bronchoconstriction after antigen challenge in rabbits.

Marked systemic hypotension accompanied by pulmonary hypertension following protamine reversal of heparin: Case report

A 44-year-old, 70-kg man with a history of anterior chest pain was treated surgically for three-vessel coronary artery bypass grafting. The patient had no history of diabetes mellitus, allergy, or previous exposure to protamine. Anesthesia was induced with 1.5 mg of fentanyl. After 12 mg of vecuronium, the trachea was intubated. Anesthesia was maintained with fentanyl, nitrous oxide, and oxygen (1:1); vecuronium was used for neuromuscular blockade. Before initiation of cardiopulmonary bypass, 2100 mg of hydrocortisone and 14 000 units of heparin sodium (Novo Industry, Copenhagen, Denmark) was given to the patient intravenously and 300 000 units of urinastatin was given to the patient during cardiopulmonary bypass. The patient underwent three-vessel coronary artery grafting without any tech-

THROMBOXANE RATHER THAN PLATELET ACTIVATING FACTOR MEDIATES PULMONARY VASOCONSTRICTION AFTER ANTIGEN CHALLENGE IN RABBITS

To investigate whether thromboxane and/or platelet activating factor (PAF) mediate the pulmonary vasoconstrictive response to antigen in vivo, we intra-arterially injected human erythrocytes as antigen into sensitized rabbits after administration of putative inhibitors: a cyclooxygenase synthetase inhibitor (indomethacin, 5 mg·kg-1), a thromboxane synthetase inhibitor (OKY 046, 10 mg·kg-1 + 100 μg·kg-1 ·min-1), and a PAF blocker (CV6209, .1 mg·kg-1). Pulmonary artery and airway pressures significantly increased after the antigen challenge in sensitized rabbits, but did not in nonsensitized rabbits. Both indomethacin and OKY046 significantly inhibited the increase in pulmonary artery pressure after the antigen challenge, while CV6209 did not. CV6209 significantly attenuated the decrease in femoral artery pressure after the antigen challenge, while neither indomethacin nor OKY046 did. There were no significant differences in the increase in airway pressure among the groups. We conclude that thromboxane rather than PAF mediates the pulmonary vasoconstriction after the antigen challenge and that mediators other than thromboxane and PAF mediate bronchoconstriction after the antigen challenge in sensitized rabbits.

Changes in the plasma histamine concentration after the administration of vecuronium bromide

Clinical symptoms of anaphylactoid reaction to muscle relaxants vary from localized flush to cardiovascular collapse. Vecuronium bromide is reported to have very little histamine releasing property. However, there are some reports of anaphylaxis or anaphylactoid reaction to vecuronium. We studied plasma histamine concentration after the intravenous injection of vecuronium to confirm the histamine release. Twenty patients were randomly allocated to one of two groups, each group comprising of 10 patients: one group was to receive vecuronium 0.1 mg·kg−1 and the other 0.2 mg·kg−1 using the priming principle. Blood samples were taken prior to and 1, 3, 5, 8 and 13 min after the administration of vecuronium. The plasma histamine concentration was measured by radioimmunoassay with monoclonal antibody. There were no significant changes in plasma histamine concentration over 13 min after the administration of vecuronium compared with the baseline value. There were also no significant differences between these two groups. We concluded that vecuronium up to 0.2 mg·kg−1 did not change the plasma histamine concentration in the patients having no previous history of allergy or atopic tendencies.