Toshiki Mizobe

In Vivo and In Vitro Studies of the Inhibitory Effect of Propofol on Human Platelet Aggregation

Background The inhibitory effects of propofol on platelet aggregation are controversial because the fat emulsion used as the solvent for propofol may affect platelet function. The effects of propofol on platelet intracellular calcium ion concentration and on aggregation were investigated. Methods Platelet aggregation was measured in 10 patients who received an intravenous infusion of propofol. Intralipos, the propofol solvent, was infused in 10 healthy volunteers and platelet aggregation were measured. The in vitro effects of propofol and Intralipos on platelets were also investigated. The inhibitory effects of various concentrations of propofol were studied. The effects of propofol on the changes in intracellular calcium level using a fluorescent dye, fura‐2, were also observed. Template bleeding time was measured to determine the effect of propofol in clinical use. Results Platelet aggregation was significantly inhibited by infusion of propofol, although bleeding time was not prolonged. Intralipos did not inhibit platelets either in vivo or in vitro. Propofol significantly inhibited platelet aggregation in vitro and at 5.81 +/‐ 2.73 micro gram/ml but not at 2.08 +/‐ 1.14 micro gram/ml. The increase of intracellular calcium concentration was inhibited both in influx and discharge of calcium. Conclusions Propofol inhibited platelet aggregation both in vivo and in vitro. Inhibition of platelet aggregation appeared to be caused by propofol itself and not by the fat emulsion. This inhibitory effect was also supported by the suppressed influx and discharge of calcium. No change in the bleeding time suggests that this inhibitory effect does not impair hemostasis clinically.

Thromboelastometry-guided intraoperative haemostatic management reduces bleeding and red cell transfusion after paediatric cardiac surgery

BACKGROUND Thromboelastometric evaluation of coagulation might be useful for prediction and management of bleeding after paediatric cardiac surgery. We tested the hypothesis that the use of a thromboelastometry-guided algorithm for blood product management reduces blood loss and transfusion requirements. METHODS We studied 78 patients undergoing paediatric cardiac surgery with cardiopulmonary bypass (CPB) for the initial 12 h after operation. Stepwise multiple linear regression was used to develop an algorithm to guide blood product transfusions. Thereafter, we randomly assigned 100 patients to conventional or algorithm-guided blood product management, and assessed bleeding and red cell transfusion requirements. RESULTS CPB time, post-bypass rotational thromboelastometry (ROTEM(®)) EXTEM amplitude at 10 min (A10), and FIBTEM-A10 were independently associated with chest tube drainage volume during the initial 12 h after operation. Discriminative analysis determined cut-off values of 30 mm for EXTEM-A10 and 5 mm for FIBTEM-A10, and estimated optimal intraoperative fresh-frozen plasma and platelet concentrate transfusion volumes. Thromboelastometry-guided post-bypass blood product management significantly reduced postoperative bleeding (9 vs 16 ml kg(-1), P<0.001) and packed red cell transfusion requirement (11 vs 23 ml kg(-1), P=0.005) at 12 h after surgery, and duration of critical care stay (60 vs 71 h, P=0.014). CONCLUSIONS Rotational thromboelastometry-guided early haemostatic intervention by rapid intraoperative correction of EXTEM-A10 and FIBTEM-A10 reduced blood loss and red cell transfusion requirements after CPB, and reduced critical care duration in paediatric cardiac surgical patients. CLINICAL TRIAL REGISTRATION UMIN Clinical Trials Registry UMIN000006832 (December 4, 2011).

Increased platelet, leukocyte, and endothelial cell activity are associated with increased coagulability in patients after total knee arthroplasty.

Background:  Orthopedic surgery, especially total knee and total hip arthroplasty, is considered a risk factor for peri‐operative venous thromboembolism.

Vertebral Artery Pseudoaneurysm: A Rare Complication of Internal Jugular Vein Catheterization

ercutaneous catheterization of the internal jugular vein is widely practiced for central venous P access and flow-directed pulmonary artery catheter placement. This approach has many wellknown advantages over the subclavian route (1). It also has the potential for several critical complications, especially accidental arterial puncture. We report a case of vertebral artery pseudoaneurysm caused by internal jugular vein puncture.

Effect of amino acid infusion on central thermoregulatory control in humans.

BackgroundAdministration of protein or amino acids enhances thermogenesis, presumably by stimulating oxidative metabolism. However, hyperthermia results even when thermoregulatory responses are intact, suggesting that amino acids also alter central thermoregulatory control. Therefore, the authors tested the hypothesis that amino acid infusion increases the thermoregulatory set point. MethodsNine male volunteers each participated on 4 study days in randomized order: (1) intravenous amino acids infused at 4 kJ · kg−1 · h−1 for 2.5 h combined with skin-surface warming, (2) amino acid infusion combined with cutaneous cooling, (3) saline infusion combined with skin-surface warming, and (4) saline infusion combined with cutaneous cooling. ResultsAmino acid infusion increased resting core temperature by 0.3 ± 0.1°C (mean ± SD) and oxygen consumption by 18 ± 12%. Furthermore, amino acid infusion increased the calculated core temperature threshold (triggering core temperature at a designated mean skin temperature of 34°C) for active cutaneous vasodilation by 0.3 ± 0.3°C, for sweating by 0.2 ± 0.2°C, for thermoregulatory vasoconstriction by 0.3 ± 0.3°C, and for thermogenesis by 0.4 ± 0.5°C. Amino acid infusion did not alter the incremental response intensity (i.e., gain) of thermoregulatory defenses. ConclusionsAmino acid infusion increased the metabolic rate and the resting core temperature. However, amino acids also produced a synchronous increase in all major autonomic thermoregulatory defense thresholds; the increase in core temperature was identical to the set point increase, even in a cold environment with amble potential to dissipate heat. In subjects with intact thermoregulatory defenses, amino acid–induced hyperthermia seems to result from an increased set point rather than increased metabolic rate per se.

Atlantoaxial subluxation in different intraoperative head positions in patients with rheumatoid arthritis

Background: Disorders of the cervical spine are often observed in patients with rheumatoid arthritis (RA). However, the best head position for RA patients with atlantoaxial subluxation in the perioperative period is unknown. This study investigated head position during general anesthesia for the patients with RA and proven atlantoaxial subluxation. Methods: During anesthesia of patients with RA and proven atlantoaxial subluxation, the authors used fluoroscopy to obtain a lateral view of the upper cervical spine in four different positions: the mask position, the intubation position, the flat pillow position, and the protrusion position. Copies of the still fluoroscopic images were used to determine the anterior atlantodental interval, the posterior atlantodental interval, and the angle of atlas and axis (C1–C2 angle). Results: The anterior atlantodental interval was significantly smaller in the protrusion position (2.3 mm) than in the flat pillow position (5.1 mm) (P < 0.05). The posterior atlantodental interval was significantly greater in the protrusion position (18.9 mm) than in the flat pillow position (16.2 mm) (P < 0.05). The C1–C2 angle was, on average, 9.3° greater in the protrusion position than in the flat pillow position (P < 0.05). Conclusion: This study showed that the protrusion position using a flat pillow and a donut-shaped pillow during general anesthesia reduced the anterior atlantodental interval and increased the posterior atlantodental interval in RA patients with atlantoaxial subluxation. This suggests that the protrusion position, which involves support of the upper cervical spine and extension at the craniocervical junction, might be advantageous for these patients.

The involvement of central cholinergic mechanisms in cardiovascular responses to intracerebroventricular and intravenous administration of thyrotropin-releasing hormone.

Intracerebroventricular (i.c.v.) administration of thyrotropin-releasing hormone (TRH) in a range from 0.1 to 100 micrograms induced a dose-related increase in blood pressure in conscious rats, whereas TRH-free acid (TRH-OH) and histidyl-proline diketopiperazine (His-Pro-DKP), metabolites of TRH, did not. The blood pressure responses to intravenous (i.v.) injection of 5 mg/Kg TRH were similar to those induced by TRH (i.c.v.). Pretreatment with atropine (50 micrograms, i.c.v.) significantly reduced the pressor effect of TRH administered through either route. Hemicholinium-3 (50 micrograms, i.c.v.), an inhibitor of choline uptake, also prevented the increase in blood pressure induced by TRH (10 micrograms, i.c.v.). These results indicate that both centrally and peripherally administered TRH have pressor effects that are mediated by central cholinergic mechanisms, probably by activating cholinergic neurons.

Autonomic hyperreflexia during labour

We present two cases of automatic hyperreflexia (AH) during labour in women with spinal cord damage, in whom AH developed before and after delivery. The AH was successfully controlled using epidural anaesthesia in Case #1, but failed in Case #2. The blood pressure was controlled with nicardipine. However, overdose of nicardipine produces vasodilatation and its side effects include headache, flushing and palpitation similar to AH1. Considering these effects, we recommend epidural anaesthesia to control AH, because epidural anaesthesia does not only reduce BP, but also blocks the noxious stimuli and relieves the symptoms of AH. Our experience suggests that the epidural catheter can be placed two to three weeks before the date of predicted childbirth, because the onset of labour in a patient with spinal cord damage is difficult to predict and can proceed very rapidly. Also, the epidural catheter is available after the delivery. We recommended the epidural catheter is maintained for 24–48 hr postpartum.RésuméLes auteurs présentent deux cas d’hyperréflexie autonome (HA) survenue pendant le travail de parturientes souffrant de lésion de la moelle épinière. Dans un cas, l’HA est apparue avant l’accouchement, et dans l’autre, après l’accouchement. Dans le premier cas, l’HA a été contrôlée efficacement avec une anesthésie épidurale. Dans le deuxième, on a réussi à contrôler la pression artérielle (PA) avec de la nicardipine. Cependant, une surdose de nicardipine a produit, comme il survient au cours de l’HA, une vasodilatation et des effets secondaires dont de la céphalée, des rougeurs et des palpitations. A cause des effets secondaires de la nicardipine, les auteurs recommandent l’anesthésie épidurale pour le contrôle de l’HA, parce que l’anesthésie épidurale ne contrôle pas seulement la PA, mais bloque aussi les stimuli nocifs et atténue les symptômes de l’HA. Les auteurs suggèrent d’insérer le cathéter épidural deux ou trois semaines avant la date prédite de l’accouchement, parce que le début du travail est difficile à prédire chez les patientes qui souffrent d’une lésion de la moelle épinière et parce qu’il peut se dérouler très rapidement. De plus le cathéter épidural reste disponible après l’accouchement. Les auteurs recommandent le maintien du cathéter pendant les 24 à 48 heures du postpartum.

Perioperative amino acid infusion improves recovery and shortens the duration of hospitalization after off-pump coronary artery bypass grafting.

Perioperative amino acid infusion helps maintain core temperature and improves patient outcomes after gynecologic and orthopedic surgery. In the present study we prospectively determined the effect of amino acid infusion on esophageal core temperature and postoperative outcomes during off-pump coronary artery bypass grafting (CABG). One-hundred-eighty consecutive patients undergoing primary elective or urgent off-pump CABG were randomly divided into two groups: the IV amino acid infusion group (4 kJ kg−1 h−1 starting 2 h before surgery) and the saline infusion group (similar period and volume of saline infusion). The esophageal core temperature at the end of surgery was 35.6 (35.3–35.8)°C [mean (95% confidence interval)] in the saline infusion group and 36.1°C (35.9–36.3)°C in the amino acid infusion group (P = 0.01). Kaplan–Meier analysis demonstrated that patients given amino acids required a significantly shorter duration of postoperative mechanical ventilation than patients given saline [median (95% confidence interval), 3.0 (2.5–3.9) vs 4.5 (3.8–5.8) h; P = 0.01]. Furthermore, intensive care unit stay [20 (19.5–38.4) vs 44 (21–45) h; P = 0.001] and days until fit for discharge from hospital [10 (9–11) vs 12 (11–13) days; P = 0.004] were significantly shorter in patients given amino acid. Perioperative amino acid infusion in patients undergoing off-pump CABG effectively minimizes intraoperative hypothermia and improves postoperative recovery.

Fructose administration increases intraoperative core temperature by augmenting both metabolic rate and the vasoconstriction threshold

Background:The authors tested the hypothesis that intravenous fructose ameliorates intraoperative hypothermia both by increasing metabolic rate and the vasoconstriction threshold (triggering core temperature). Methods:Forty patients scheduled to undergo open abdominal surgery were divided into two equal groups and randomly assigned to intravenous fructose infusion (0.5 g · kg−1 · h−1 for 4 h, starting 3 h before induction of anesthesia and continuing for 4 h) or an equal volume of saline. Each treatment group was subdivided: Esophageal core temperature, thermoregulatory vasoconstriction, and plasma concentrations were determined in half, and oxygen consumption was determined in the remainder. Patients were monitored for 3 h after induction of anesthesia. Results:Patient characteristics, anesthetic management, and circulatory data were similar in the four groups. Mean final core temperature (3 h after induction of anesthesia) was 35.7° ± 0.4°C (mean ± SD) in the fructose group and 35.1° ± 0.4°C in the saline group (P = 0.001). The vasoconstriction threshold was greater in the fructose group (36.2° ± 0.3°C) than in the saline group (35.6° ± 0.3°C; P < 0.001). Oxygen consumption immediately before anesthesia induction in the fructose group (214 ± 18 ml/min) was significantly greater than in the saline group (181 ± 8 ml/min; P < 0.001). Oxygen consumption was 4.0 l greater in the fructose patients during 3 h of anesthesia; the predicted difference in mean body temperature based only on the difference in metabolic rates was thus only 0.4°C. Epinephrine, norepinephrine, and angiotensin II concentrations and plasma renin activity were similar in each treatment group. Conclusions:Preoperative fructose infusion helped to maintain normothermia by augmenting both metabolic heat production and increasing the vasoconstriction threshold.