Effect of peak inspiratory flow on gas exchange, pulmonary mechanics, and lung histology in rabbits with injured lungs

Purpose The aim of this study was to evaluate, using a rabbit model, the little-known effect of different levels of peak inspiratory flow on acutely injured lungs. Methods Fourteen male rabbits (body weight, 2711 ± 146 g) were anesthetized and their lungs were injured by alveolar overstretch with mechanical ventilation until Pa_O2 was reduced below 300 mmHg. Injured animals were randomly assigned to: the P group—to receive pressure-regulated volume-control ventilation (PRVCV; n = 7); and the V group—to receive volume-control ventilation (VCV; n = 7). Other ventilator settings were: fraction of inspired oxygen (FI_O2), 1.0; tidal volume, 20 ml·kg⁻¹; positive end-expiratory pressure (PEEP) 5 cmH₂O; and respiratory rate, 20 min⁻¹. The animals were thus ventilated for 4 h. Throughout the protocol, ventilatory parameters and blood gas were measured every 30 min. After the protocol, the lung wet-to-dry ratio and histological lung injury score were evaluated in the excised lungs. Results Throughout the protocol, peak inspiratory flow and mean inspiratory flow values in the P group were significantly higher than those in the V group (26.7 ± 5.0 l·min⁻¹ vs 1.2 ± 0.2 l·min⁻¹, and 4.3 ± 0.3 l·min⁻¹ vs 1.1 ± 0.1 l·min⁻¹; P < 0.05). The wet-to-dry ratio in the P group was also significantly higher than that in the V group (7.7 ± 0.9 vs 6.3 ± 0.5; P < 0.05). More animals in the P group than in the V group had end-of-protocol Pa_O2/FI_O2 ratios below 200 mmHg (43% vs 0%; P = 0.06). Conclusion In rabbits with injured lungs, high peak inspiratory flow with high tidal volume (V_T) reduces the Pa_O2/FI_O2 ratio and increases the lung wet-to-dry ratio.     

Recovery from Fontan circulation failure by application of continuous negative extrathoracic pressure

A 2-year-old girl developed lethal circulatory failure, general edema, and hepatic dysfunction in an acute phase after total cavopulmonary connection, a Fontan-type operation. Application of continuous negative extrathoracic pressure (CNEP) with a cuirass ventilator at −4 cmH₂O under spontaneous respiration dramatically improved hemodynamics, with systolic arterial pressure increasing from 82 mmHg to 90 mmHg, and central venous pressure decreasing from 15 mmHg to 13 mmHg; also, urine output increased, from 1.6 ml·kg⁻¹·h⁻¹ to 6.4 ml·kg⁻¹·h⁻¹. Improvements in hepatic function and fluid retention (reduction of pleural fluid and ascites) were also observed. The patient was successfully weaned from CNEP after 5 days. CNEP is an easily applicable, noninvasive tool to reduce pulmonary impedance, and is specifically useful to improve hemodynamics in patients after a Fontan-type operation. Our result suggests that CNEP may represent a first-line option to save patients from critical circulatory failure after a Fontan-type operation.     

Nitric oxide inhalation increases oxygen delivery after cardiovascular surgery in adult patients whether or not they have pulmonary hypertension

Purpose The purpose of this study was to quantify the increase in oxygen delivery (DO₂) produced by nitric oxide (NO) inhalation, and to clarify whether NO inhalation might be effective in adult patients after cardiovascular surgery whether or not they have pulmonary hypertension (PH). Methods The study was done on 26 adult patients after cardiovascular surgery. The indications for NO inhalation were postoperative hypoxic respiratory failure (POHRF) with or without PH. NO was administered via a premixing system or via a side-stream system. The dose was adjusted to between 1 and 10 (5.7±2.0) (mean±SD) ppm. Data were obtained just before and within 120 min after the initiation of NO inhalation. We initially analyzed the data from all the patients together and then compared data from two groups made up from just 22 of the 26 patients: 14 patients without PH whose PaO₂/FiO₂ before NO inhalation was less than 200 mmHg (simple POHRF group), and 8 patients who had both POHRF and PH (systolic pulmonary arterial pressure higher than 40 mmHg) (POHRF with PH group). Results In the original group of 26 patients, significant improvements were observed in PaO₂, PaO₂/FiO₂, CI, SPAP, CaO₂, DO₂I, and SvO₂ during NO inhalation. The increase in DO₂I was 68 ml·min⁻¹·m⁻² (+19.5%). PaO₂, PaO₂/FiO₂, CaO₂, DO₂I, and SvO₂ increased significantly in both groups. The increase in DO₂I was 60 ml·min⁻¹·m⁻² (+18.9%) in the simple POPHRF group and 79ml·min⁻¹·m⁻² (+18.0%) in the POHRF with PH group. Conclusion NO inhalation increases DO₂ by approximately 20% in adult patients after cardiovascular surgery, irrespective of whether or not they have pulmonary hypertension.     

Hemodynamic effects of KRN2391 (potassium channel opener) in halothane-anesthetized dogs

The cardiovascular responses to an infusion of KRN2391, a potassium channel opener, was studied in halothane-anesthetized dogs. Intravenous administration of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ for 60 min produced dose-dependent decreases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) associated with dose-dependent increases in the cardiac index (CI) and stroke volume index (SVI) but was not accompanied by an increase in heart rate (HR). The maximum decrease in MAP during the infusion of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −13±7% (P<0.01) and −37±10% (P<0.01), respectively. The maximum reduction in SVR after 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −20±11% (P<0.01) and −60±16% (P<0.01), respectively. A KRN2391 infusion of 1.0 and 5.0 μg·kg⁻¹·min⁻¹ increased Cl a maximum of 11±13% (P<0.05) and 65±33% (P<0.01), respectively. KRN2391 1.0 μg·kg⁻¹·min⁻¹ showed a tendency to increase SVI but this change was not significant, KRN2391 5.0 μg·kg⁻¹·min⁻¹, however, produced a significant increase in SVI. The present results demonstrate that the decrease in MAP and the increases in CI and SVI caused by KRN2391 are due to a reduction in the afterload. Therefore, we conclude that these cardiovascular profiles of KRN2391 may be benificial in perioperative uses including the control of systemic blood pressure and the treatment of hypertension during halothane anesthesia in clinical practice.     

Total body propofol clearance (TBPC) after living-donor liver transplantation (LDLT) surgery is decreased in patients with a long warm ischemic time

Metabolic capacity after liver transplant surgery may be affected by the graft size and by hepatic injury during the surgery. This study was carried out to investigate the postoperative total body propofol clearance (TBPC) in living-donor liver transplantation (LDLT) patients and to investigate the major factors that contribute to decreased postoperative TBPC in LDLT patients. Fourteen patients scheduled for LDLT were included in this study. Propofol was administered at a rate of 2.0 mg·kg⁻¹·h⁻¹ as a sedative in the intensive care unit (ICU) setting. To calculate TBPC, propofol arterial blood concentration was measured by HPLC. Five variables were selected as factors affecting postoperative TBPC; bleeding volume (BLD), warm ischemic time (WIT), cold ischemic time (CIT), graft weight/standard liver volume ratio (GW/SLV), and portal blood flow after surgery (PBF). After factor analysis of six variables, including TBPC, varimax rotation was carried out, and this yielded three interpretable factors that accounted for 75.5% of the total variance in the data set. TBPC, WIT, CIT, and BLD were loaded on the first factor, PBF on the second factor, and GW/SLV on the third factor. The adjusted correlation coefficient between TBPC and WIT showed the highest value (r = −0.61) in the first factor. The LDLT patients were divided into two groups according to WIT; group A (WIT > 100 min) and group B (WIT < 100 min). Mean TBPC values in group A and group B were 14.6 ± 2.1 and 28.5 ± 4.1 ml·kg⁻¹·min⁻¹, respectively (P < 0.0001). These data suggest that LDLT patients with a long WIT have a risk of deteriorated drug metabolism.     

Comparison of heart rate changes after neostigmine-atropine administration during recovery from propofol-N2O and isoflurane-2O anesthesia

Purpose. Propofol augments the reduction of heart rate (HR) in combination with cholinergic agents and attenuates the HR response to atropine. We examined whether propofol anesthesia was associated with an increased incidence and extent of bradycardia after neostigmine-atropine administration compared with the effects of isoflurane anesthesia. Methods. Thirty-six adult patients were randomly assigned to two groups (n = 18 each): the propofol group patients were anesthetized with propofol (5–10 mg·kg⁻¹·h⁻¹)-₂O-fentanyl, and the isoflurane group patients were anesthetized with isoflurane (0.5%–1.0%)-₂O-fentanyl. When surgery was completed, anesthetics were discontinued, and then a mixture of neostigmine 0.05 mg·kg⁻¹ and atropine 0.02 mg·kg⁻¹ was injected intravenously over 20 s. Blood pressure (BP) and HR were measured noninvasively at 1-min intervals for 10 min. Results. At the completion of the surgery, the average infusion rate of propofol was 6.2 ± 1.7 mg·kg⁻¹·h⁻¹, and the average inspired concentration of isoflurane was 0.73 ± 0.15%. Immediately before the neostigmine-atropine injections, HR and mean BP were similar in the two groups. The maximum increase in HR after the neostigmine-atropine injections was significantly less in the propofol group than in the isoflurane group (16 ± 9 and 34 ± 6 beats·min⁻¹, respectively, P < 0.01). The subsequent maximum decrease in HR was greater in the propofol group than in the isoflurane group (−9 ± 4 and −5 ± 4 beats·min⁻¹, respectively; P < 0.01). The incidence of bradycardia (HR < 50 beats·min⁻¹) after neostigmine-atropine injection was greater in the propofol group than in the isoflurane group (61% and 28%, respectively; P < 0.01). Conclusion. We conclude that propofol anesthesia attenuates the initial increases in HR, enhances the subsequent decreases in HR, and increases the incidence of bradycardia after neostigmine-atropine injections compared with the effects of isoflurane anesthesia. Received: May 21, 2001 / Accepted: August 29, 2001     

Prevention of postoperative nausea and vomiting in children following adenotonsillectomy,using tropisetron with or without low-dose dexamethasone

Purpose Postoperative nausea and vomiting (PONV) after adenotonsillectomy in children is, in spite of the prophylactic administration of tropisetron, still a frequent event. The aim of this study was to evaluate the benefit of the additional systemic administration of low-dose dexamethasone (0.15 mg·kg⁻¹) for the prevention of PONV. Methods With hospital ethics committee approval, we investigated children undergoing adenotonsillectomy receiving tropisetron (0.1 mg·kg⁻¹; maximum dose, 2 mg) or tropisetron (0.1 mg·kg⁻¹; maximum dose, 2 mg) plus dexamethasone (0.15 mg·kg⁻¹; maximum dose, 6 mg) intraoperatively. The incidence of vomiting episodes and the need for postoperative analgesics were recorded. Patient data were analyzed using the t-test and the χ² test (significance level of P = 0.05). Data values are means ± SD. Results Ninety children (39 girls and 51 boys), aged 5.6 ± 2.8 years and weighing 21.9 ± 8.8 kg, were enrolled in the study. The overall incidence of vomiting was 38.9% within the first 24 h (67 vomiting events) and 44.4% within 48 h postoperatively (87 vomiting events). The incidence of vomiting in the tropisetron-only group was 53.3% (24/45) at 24 h and 60% (27/45) at 48 h (24 h: P < 0.001 and 48 h: P = 0.04) and 24.4% (11/45) at 24 h and 28.9% (13/45) at 48 h in the tropisetron-dexamethasone group. The need for postoperative nalbuphine was double in patients treated with tropisetron-dexamethasone (0.61 mg ± 0.36 mg·kg⁻¹·48 h⁻¹) compared to that in patients receiving only tropisetron (0.31 mg ± 0.28 mg·kg⁻¹·48 h⁻¹; P < 0.0001). Conclusion A low-dose bolus of dexamethasone (0.15 mg·kg⁻¹) in combination with tropisetron, compared to tropisetron alone, considerably reduced the incidence of vomiting in children following pediatric adenotonsillectomy.     

Net Fluxes Over Working Thigh of Hormones,Growth Factors and Biomarkers of Bone Metabolism During Short Lasting Dynamic Exercise

The purpose of this study was to evaluate the responses of hormones, growth factors, and biomarkers involved in bone and muscle metabolism during exercise and in recovery. One leg knee-extension exercise and concomitant sampling from the artery and vein were performed. In 12 healthy individuals (6 men and 6 women; age 21–36 years) blood was drawn from the femoral artery and vein at rest, after 10 minutes warm-up, after 15 minutes work at 61% of peak one leg VO₂, and after 5 minutes work at peak one leg VO₂, as well as 5, 30, and 60 minutes in recovery. Blood flow in the femoral vein was measured using the thermodilution technique. Arteriovenous differences were measured over working thigh for growth hormone (GH), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGF BP3), parathyroid hormone (PTH) and bone biomarkers, i.e., the carboxyterminal propeptide of type I procollagen (PICP), the carboxyterminal cross-linked telopeptide of type I collagen (ICTP), osteocalcin, and bone-specific alkaline phosphatase (b-ALP). There was an uptake of GH (3.1 ± 1.2 mU · min⁻¹, P < 0.001; mean ± SE) over thigh during exercise and a release of IGF-I at the end of exercise (60 ± 36 μg · min⁻¹; P < 0.01). PICP was also released after the maximal exercise (23 ± 12 μg · min⁻¹; P < 0.01) as well as ICTP (0.5 ± 0.3 μg · min⁻¹; P < 0.05) and b-ALP (0.2 ± 0.1 μkat · min⁻¹; P < 0.05). Osteocalcin, IGF BP3, and PTH revealed no clearcut pattern. In the present study, exercise induces endocrine changes which point to anabolic effects on muscle and bone tissue. Received: 12 February 1996 / Accepted: 6 June 1996     

Carbon dioxide exhalation temporarily increases during electroconvulsive therapy

Electroconvulsive therapy induces hypermetabolism and elevates oxygen and energy demands, while more carbon dioxide is produced than usual. The purpose of the present study was to determine the elevated carbon dioxide exhalation and the adequate ventilation volume during electroconvulsive threrapy. Carbon dioxide exhalation during an electrically induced seizure was continuously monitored by capnography and spirography in 15 patients with endogenous depression. A laryngeal mask airway was used to measure the airway gas flow. Data were collected during a total of 80 electroconvulsive therapy trials. The carbon dioxide exhalation at 1 min after electrical stimulation was higher than the control value (2.8 ± 0.4 versus 2.3 ± 0.3 ml·min⁻¹·kg⁻¹, mean ± SD; P < 0.05). The ventilation volume was increased for 3 min after the electrical stimulation to maintain the end-tidal carbon dioxide partial pressure at 35–40 mmHg. The results showed that increasing the ventilation volume by approximately 20% may be necessary to compensate for the increased carbon dioxide exhalation during electroconvulsive therapy. Presented in part at the 49th annual meeting of the Japanese Society of Anesthesiologists, kobe, Japan.     

Effect of infraorbital nerve block under general anesthesia on consumption of isoflurane and postoperative pain in endoscopic endonasal maxillary sinus surgery

Purpose. The efficacy of infraorbital nerve block in reducing isoflurane consumption and postoperative pain was evaluated in patients undergoing endoscopic endonasal maxillary sinus surgery (ESS) under general anesthesia. Methods. Fifty patients were randomly allocated to either the block group (n = 15) or the nonblock group (n = 25). After the establishment of general anesthesia with isoflurane, nitrous oxide, and oxygen, the patients received infraorbital nerve block with 1.0 ml of either 0.5% bupivacaine (block group) or normal saline (nonblock group) administered into the soft tissue in front of the infraorbital foramen. Systolic blood pressure during anesthesia and surgery was maintained at 85–90 mmHg by adjusting the inspiratory concentration of isoflurane, and its consumption was evaluated in both groups. Pain intensity at 15 min after the end of anesthesia was also evaluated on a five-point pain scale. Results. The consumption of isoflurane under a fresh gas flow of 6 l·min⁻¹ was 17.3 ± 6.5 ml·kg⁻¹·h⁻¹ (mean ± SD) in the block group and 27.4 ± 9.4 ml·kg⁻¹·h⁻¹ in the nonblock group during surgery (P < 0.001). Nicardipine was required during surgery less frequently in the block group than in the nonblock group (P < 0.01). Postoperative pain intensity was lower in the block group than in the nonblock group (P < 0.01). Conclusion. General anesthesia combined with infraorbital nerve block is effective in reducing the consumption of isoflurane and postoperative pain intensity in ESS. Received: April 4, 2000 / Accepted: February 13, 2001     

Comparison of renal function under deliberate hypotension during epidural plus light-enflurane anesthesia and during enflurane anesthesia

We compared the effects of deliberate hypotension induced with trimethaphan on renal function and renal tubular damage under combined epidural and light-enflurane anesthesia (epidural group) and enflurane anesthesia alone (enflurane group). The mean arterial blood pressure was maintained at 50–55 mm Hg for 2.5 h in both groups using continuous infusion of trimethaphan. The urine volume and free water clearance were significantly greater in the epidural group than in the enflurane group [1.8±1.8 (SD)vs 0.4±0.3 ml·kg⁻¹·h⁻¹ and 0.81±1.30vs −0.15±0.22 ml·min⁻¹, respectively] (P<0.05). The creatinine clearance and fractional sodium excretion rate did not differ significantly between the two groups. Urinary excretion of norepinephrine was significantly less in the epidural group than in the enflurane group (P<0.05); however, epinephrine excretion did not differ. Urinary excretion ofN-acetyl-β-d-glucosaminidase was significantly less in the epidural group than in the enflurane, group (4.2±2.5vs 12.2±4.6 U·g⁻¹ CR) (P<0.01). The plasma antidiuretic hormone concentration was significantly lower in the epidural group compared to the enflurene group (13±23vs 57±42 pg·ml⁻¹) (P<0.05). No significant difference in plasma atrial natriuretic peptide concentration was found between the groups. We conclude that renal function during trimethaphan-induced hypotension is better maintained under epidural plus light-enflurane anesthesia than under enflurane anesthesia alone.     

Comparison between in vivo and in vitro pharmacokinetics of succinylcholine in humans

Purpose. To compare the in vivo and in vitro pharma-cokinetics of succinylcholine (SCh) in humans. Methods. A bolus of SCh 1 mg·kg⁻¹ (n = 7) or 2 mg·kg⁻¹ (n = 11) was given to 18 patients anesthetized with thiopental. Arterial blood samples for determination of in vivo SCh concentrations were collected every 30 s for 5 min. Another 20-ml blood sample was obtained before induction of anes-thesia for determination of in vitro SCh. Concentrations of SCh were measured by high-performance liquid chromato-graphy. In vivo and in vitro concentrations of SCh vs time data were analyzed by the one-compartment model. Results. The respective in vivo and in vitro pharmacokinetic parameters (SCh 1 mg·kg⁻¹ vs SCh 2 mg·kg⁻¹) were as follows: Plasma clearance was 4.17 ± 2.37 and 1.85 ± 0.28 l·min⁻¹, P < 0.05, vs 2.91 ± 2.01 and 1.27 ± 0.43 l·min⁻¹, P < 0.05. Elimination half-life was 25.4 ± 10.6 and 47.4 ± 5.4 s, P < 0.002 vs 26.3 ± 10.0 and 75.2 ± 21.8 s, P < 0.00005. Conclusion. These results suggest that the rapid disap-pearance of SCh from the circulation is due to diffusion out of the blood vessels rather than to enzymatic hydrolysis. Received for publication on August 31, 1998; accepted on May 11, 1999     

Continuous measurement of oxygen consumption using the reversed fick method

We developed a continuous oxygen consumption (Vo₂) measurement system employed the reversed Fick method, in which Vo₂ in computed from continuously measured sured arterial and mixed venous oxygen saturation assed by pulse oximetry and mixed venous oximetry, respectively, and cardiac output by the heat deprivation technique. This system was compared with the conventional intermittent reversed fick method in 7 patients during surgery and with indirect calorimetry in 4 intensive care unit (ICU) patients. The Vo₂ measured by the continuous reversed Fick method showed a high correlation with those simultaneously measured by the intermittent Fick method (r=0.97,P<0.01) and by indirect calorimetry (r=0.74,P<0.01). The 95% confidence limits (bias±2 SD) of the continuous reversed Fick method were −0.6±45 ml·min⁻¹ with the intermittent Fick method and −31±56 ml·min⁻¹ with indirect calorimetry. The continuous Fick method is in satisfactory agreement with the conventional methods for the measured of Vo₂ and potentially allows for convenient assessment of Vo₂ in critically ill patients. This study was supported in part by Grants-in-Aid for the Encouragement of Young Scientists 01771185 and 04857171 from the Ministry of Education, Science and Culture of Japan     

Effect of external high-frequency oscillation on severe cardiogenic pulmonary edema

Effective gas exchange can be maintained in animals without endotracheal intubation using external high-frequency oscillation (EHFO). The aim of this study was to evaluate the effect of EHFO in patients with respiratory failure due to severe cardiogenic pulmonary edema. Seven patients were ventilated with EHFO for 2h at 60 oscillations·min⁻¹, with a cuiras pressure of 36 cmH₂O (−26 to +10) and an inspiratory to expiratory ratio of 1:1, with EHFO. Blood gas values and hemodynamic parameters were measured. Significant increases were noted in cardiac index (2.3±0.5 to 2.5±0.5 l·m⁻²;P<0.05), stroke volume index (24±7 to 28±8 ml·m⁻²;P<0.05), and arterial O₂ pressure (Pao₂) (70±4 to 95±23 mmHg;P<0.01) without a change in pulmonary artery wedge pressure at 1 h after EHFO. The respiratory rate decreased from 28±3 to 22 ±3 breaths·min⁻¹ at 5 min after the termination of EHFO (P <0.01). Arterial CO₂ pressure (Paco₂) did not, however, decrease. Increased stroke volume without a change in pulmonary artery wedge pressure (preload) suggests either improved inotropic function of the left ventricle or reduced left ventricular afterload with EHFO. The use of EHFO may be effective not only for gas exchange but also for left ventricular function in patients with severe cardiogenic pulmonary edema.     

Pharmacokinetic profile of propofol after a single-dose injection during general anesthesia in Japanese adults

Purpose. To determine the pharmacokinetic parameters of propofol after a single-dose injection in Japanese adults. Methods. This study was carried out in adult patients who underwent minor surgery under general anesthesia with sevoflurane. We injected 1.0, 1.5, or 2.0 mg·kg⁻¹ of propofol at a constant rate using a syringe pump. Arterial blood samples were taken for 480 min after the administration of propofol. The whole-blood concentration of propofol was determined with gas chromatography, and a time–blood concentration curve was analyzed by a two-compartment open-model analysis and a model-independent analysis. Results. The half-lives of the central and peripheral compartment (t _1/2α and t _1/2β) were 2.26 ± 0.69 and 47.9 ± 22.1 min, respectively. The volume of the central compartment (V_c) was 0.582 ± 0.170 l·kg⁻¹, and the apparent volume of distribution at a steady state (V_dss) was 2.62 ± 1.06 l·kg⁻¹. The total body clearance (Cl) and mean residence time (MRT) were 53.7 ± 11.9 ml·min⁻¹·kg⁻¹ and 98.1 ± 16.4 min, respectively. Conclusions. Among the pharmacokinetic parameters determined in Japanese adults, t _1/2α, t _1/2β, and Vc were similar, V_dss was smaller, and Cl was larger, as compared with values in Caucasians. These findings suggest that propofol could be eliminated well during minor surgery in Japanese adults. Received: January 27, 1999 / Accepted: March 31, 2000     

Effect of Ono-EI-600 elastase inhibitor on high-tidal-volume-induced lung injury in rats

We tested the effect of Ono-EI-600, an elastase inhibitor that suppresses cytokine release, on ventilator-induced lung injury in a rat model. After Wistar rats (aged 8–11 weeks) were anesthetized and tracheostomized, they were randomly assigned to four groups: high tidal volume (V_T) group (H group: n = 10) receiving peak inspiratory pressure (PIP) 30 cmH₂O for 240 min; high V_T with drug group (HD group: n = 10) receiving the same ventilation settings as H group and also intravenous infusion 10 mg·kg⁻¹·h⁻¹ of Ono-EI-600 during the protocol; the lower V_T group (L group: n = 5) receiving PIP 10 cmH₂O for 240 min; and control group (C group: n = 5) receiving the same ventilation as L group for 30 min. The cytokine levels (IL-6 and CINC-1) in the bronchoalveolar lavage fluid (BALF) of the H group were significantly higher than those of the C and L groups (P < 0.05). However, for the H and HD groups, no differences were found in arterial blood gas data, cytokine levels in BALF, and histological injury scores. Our experiment provided no evidence that elastase inhibitor Ono-EI-600 protects against lung injury induced by high V_T ventilation.     

Effect of low-dose infusion of prostaglandin E1 on vecuronium-induced neuromuscular blockade

The effect of low-dose (20 ng·kg⁻¹·min⁻¹) infusion of prostaglandin E₁ (PGE₁) on vecuronium-induced neuromuscular blockade was studied. The study population consisted of 24 elderly patients (65–75 years old) and 24 younger adult patients (25–56 years old). They were randomly assigned to the control and PGE₁ groups. The steady-state dose requirement (SSDR) of vecuronium was derived from ondemand infusion of the drug which produced a stable twitch height of 20% of its baseline reading, and recovery time after steady-state infusion was defined as the time for recovery from twitch height from 25% to 75%. The patients in the PGE₁ group received an infusion of PGE₁ 20 ng·kg⁻¹·min⁻¹, while those in the control group received an infusion of normal saline. The SSDR (23.2±9.1 and 34.2±5.9 μg·kg⁻¹. hr⁻¹, respectively;P=0.02) was significantly less and the recovery time (35.0±9.5 and 19.9±4.2 min, respectively;P=0.01) was significantly longer in the elderly than in the younger patients. However, low-dose infusion of PGE₁ significantly increased the SSDR (23.2±9.1 to 37.4±3.7 μg· kg⁻¹·hr⁻¹;P=0.01) and shortened the recovery time (35.0±9.5 to 23.5±4.0 min;P=0.02) in elderly patients. We concluded that low-dose infusion of PGE₁ is effective in preventing the prolonged action of vecuronium in elderly patients.     

Before-after study of a restricted fluid infusion strategy for management of donor hepatectomy for living-donor liver transplantation

Purpose  Intraoperative fluid infusion strategy remains controversial. Many animal model studies have shown that restricted fluid infusion reduces blood loss, though reports on this topic in humans are rare. The purpose of this study was to determine the effects on volume of blood loss of a restricted fluid infusion strategy for hepatectomy in donors for livingdonor liver transplantation. Methods  A before-after study design was used with prospective consecutive data collection. A total of 22 patients who underwent living-donor hepatectomy were enrolled. Eleven patients who were managed before the implementation of restricted-volume fluid administration comprised the standard-volume group, and 11 who were evaluated after the implementation of the restricted-volume infusion strategy comprised the restricted-volume group. In the standard-volume group, the donors were given 10 ml·kg⁻¹·h⁻¹ of lactated Ringer’s solution and additional plasma expander corresponding to blood loss. In the restricted-volume group, the donors received 5 ml·kg⁻¹·h⁻¹ of lactated Ringer’s solution until the resection of the hepatic graft, followed by 15 ml·kg⁻¹·h⁻¹ of lactated Ringer’s solution after the completion of resection until the end of the operation. Results  Intraoperative blood loss was less in the restricted-volume group (445 ± 193 ml) than in the standard-volume group (1331 ± 602 ml; P < 0.01). Intraoperative fluid infusion was also less in the restricted-volume group (4130 ± 563 ml) than in the standard-volume group (5634 ± 1260 ml; P < 0.01). There were no differences in length of hospital stay or side effects between the two groups. Conclusion  Our restricted-volume strategy reduced blood loss and had no adverse effects during living-donor hepatectomy.     

Dose-dependent effects of repeated ketamine administration on muscarinic acetylcholine receptors in the mouse forebrain

To study the effects of repeated ketamine administration (0: saline, 12.5, 25, and 50 mg·kg⁻¹ every 3 days for a total of five times, subcutaneously) on the central muscarinic acetylcholine receptors (mAchRs), receptor binding assays of mAchR were carried out in the forebrain of mice, using [³H]quinuclidinyl benzilate ([³H]QNB) as a ligand. We also examined whether repeated ketamine administration could modify the sensitivity to scopolamine (0.5 mg·kg⁻¹) (a muscarinic antagonist). Repeated ketamine administration produced a significant increase in the receptor density values (Bmax) for [³H]QNB (1520±51 fmol·mg protein⁻¹ for the control group, 1650±43 for the 12.5 mg·kg⁻¹ group, 1966±70 for the 25 mg·kg⁻¹ group and 2064±125 for the 50 mg·kg⁻¹ group) (P<0.05, when the 25 mg·kg⁻¹ and 50 mg·kg⁻¹ groups were compared to the control group) without any change in apparent affinity. Repeated ketamine reduced scopolamine-induced hyperlocomotion at 50 mg·kg⁻¹ (P<0.05). We conclude that repeated ketamine administration produces up-regulation of mAchRs, which is probably associated with the altered Ach transmission of the central nervous system.     

Preoperative estimation of pulmonary extravascular thermal volume in patients undergoing pneumonectomy

Pulmonary extravascular thermal volume (PETV) was measured during pulmonary artery occlusion in 18 patients preoperatively and 7 patients postoperatively who were undergoing pneumonectomy. We found that the PETV decreased from 6.6±2.3 ml·kg⁻¹ before occlusion to 4.1±1.6 ml·kg⁻¹ during occlusion. There was a significant correlation between the PETVs before and during occlusion multiplied by the fraction of pulmonary perfusion (r=0.77,P<0.001). Although the PETV increased in two patients and decreased in four within 48 h after pneumonectomy, it returned to the value during occlusion at 3 weeks after pneumonectomy in seven patients. There was a significant correlation between the PETV during occlusion and that at 3 weeks after pneumonectomy (r=0.66,P<0.05). In conclusion, PETV during pulmonary artery occlusion is a reliable baseline value in the assessment of postoperative pneumonectomy values.