Regulating Antifreeze Activity through Water: Latent Functions of the Sugars of Antifreeze Glycoprotein Revealed by Total Chemical Synthesis.

Antifreeze glycoprotein (AFGP), which inhibits the freezing of water, is highly O-glycosylated with a disaccharide, d-Galß1-3-d-GalNAcα (GalGalNAc). To elucidate the function of the sugar residues for antifreeze activity at the molecular level, we conducted a total chemical synthesis of partially sugar deleted AFGP derivatives, and unnatural forms of AFGPs incorporating glucose (Glc)-type sugars instead of galactose (Gal)-type sugars. These elaborated AFGP derivatives demonstrated that the stereochemistry of each sugar residue on AFGPs precisely correlates with the antifreeze activity. A hydrogen-deuterium exchange experiment using synthetic AFGPs revealed a different dynamic behavior of water around sugar residues depending on the sugar structures. These results indicate that sugar residues on AFGP form a unique dynamic water phase that disturbs the absorbance of water molecules onto the ice surface, thereby inhibiting freezing.

Unexpected deposits in the anesthetic circuit: a possible cause of PEEP/Pmax valve malfunction.

PEEP is regulated by the internal PEEP/maximum peak inspiratory pressure limit (Pmax) valve. Malfunctioning of the PEEP/Pmax valve can result in the creation of unintentional or unstable PEEP, and a reduction of inspired tidal volume. Some of our Dräger Fabius® anesthesia machines were noted to exhibit changes in expiratory waveforms and unstable PEEP during general anesthesia. We considered that the cause was associated with PEEP/Pmax valve malfunction, and then investigated the problems in collaboration with the manufacturer. Seven of the 22 Dräger Fabius® anesthesia workstations at our department exhibited problems with their PEEP/Pmax valves. We replaced the PEEP membrane and sealing washers in these seven anesthesia machines, and the problems were temporarily resolved. After a short interval, however, one of the seven machines began to show a similar phenomenon. We then asked the manufacturer to overhaul the PEEP/Pmax valve and the entire breathing circuit of the machine. On close investigation, we found that the valve components and the internal surface of the breathing circuit were contaminated with unexpected deposits. The build-up of deposits occurred within a year after the previous regular inspection. Our troubleshooting process determined the issue with the PEEP/Pmax valve, which could go unnoticed because the valve is encased inside the breathing circuit, and requires disassembly for close inspection. Our findings should raise awareness regarding the importance of the preventive maintenance cycle as a safety precaution to keep the anesthetic circuit free of unexpected contamination.

Anesthesia management of arthroscopic ankle arthrodesis for a hemophilia patient after living-donor liver transplantation.

Hemophilia is an X-linked recessive inherited coagulation disorder. We report the anesthesia management of a hemophilia patient who underwent arthroscopic ankle arthrodesis after living-donor liver transplantation due to cirrhosis. The 35-year-old male patient with hemophilia B was diagnosed with cirrhosis due to hepatitis C virus at the age of 23 years and underwent biologically-related partial liver transplantation at the age of 29 years. As a result, the activity of factor IX activity became normal and blood product treatment became unnecessary, but the patient required long-term immunosuppression. Perioperative coagulation factor activity monitoring was performed and an immunosuppressive drug that had been preoperatively administered were continued. General anesthesia was administered by inhalation. There was no significant fluctuation in perioperative factor IX activity. This case illustrates that even in patients with hemophilia B after living-donor liver transplantation undergoing an orthopedic surgical procedure, anesthesia management can safely be performed without perioperative coagulation factor replacement.

Total Synthesis of O-GalNAcylated Antifreeze Glycoprotein using the Switchable Reactivity of Peptidyl-N-pivaloylguanidine.

Antifreeze glycoprotein (AFGP) is an O-glycoprotein that displays antifreeze activity through depression of the freezing point of water. GalNAc is a core sugar structure of AFGP, and contributes to induce antifreeze activity of this glycoprotein. However, the general functional role that this sugar plays at the molecular level is still unknown. To elucidate this, it is essential to determine the relationship between structure and activity of O-GalNAcylated AFGP using homogeneous glycoproteins. Thus, the total synthesis of homogeneous O-GalNAcylated AFGP was conducted by using a unique peptide derivative: peptidyl-N-pivaloylguanidine. It was found that peptidyl-N-pivaloylguanidine is an "unreactive" peptide in peptide coupling reactions but is interconvertible with a "reactive" peptide-α-thioester by means of a simple treatment under buffer condition at pH=7 to 8. The unique switchable reactivity of peptidyl-N-pivaloylguanidine enabled an efficient sequential peptide coupling strategy. By using this strategy, various lengths of homogeneous O-GalNAcylated AFGP were synthesized, including one that was 120 amino acids in length, with 40 O-GalNAcylation sites. The structural analysis by circular dichroism spectroscopy and evaluation of the antifreeze activity of the synthetic AFGP(GalNAc)s revealed that the simple O-glycosylation with GalNAc is essential for both structural and functional basis of AFGP to exhibit antifreeze activity.

Reliability of cardiac output measurements using LiDCOrapid™ and FloTrac/Vigileo™ across broad ranges of cardiac output values.

Knowing a patient's cardiac output (CO) could contribute to a safe, optimized hemodynamic control during surgery. Precise CO measurements can serve as a guide for resuscitation therapy, catecholamine use, differential diagnosis, and intervention during a hemodynamic crisis. Despite its invasiveness and intermittent nature, the thermodilution technique via a pulmonary artery catheter (PAC) remains the clinical gold standard for CO measurements. LiDCOrapid™ (LiDCO, London, UK) and FloTrac/Vigileo™ (Edwards Lifesciences, Irvine, CA) are less invasive continuous CO monitors that use arterial waveform analysis. Their calculations are based on arterial waveform characteristics and do not require calibration. Here, we evaluated LiDCOrapid™ and FloTrac/Vigileo™ during off-pump coronary artery bypass graft (OPCAB) and living-donor liver transplantation (LDLT) surgery. This observational, single-center study included 21 patients (11 OPCAB and 10 LDLT). We performed simultaneous measurements of CO at fixed sampling points during surgery using both devices (LiDCOrapid™ version 1.04-b222 and FloTrac/Vigileo™ version 3.02). The thermodilution technique via a PAC was used to obtain the benchmark data. LiDCOrapid™ and FloTrac/Vigileo™ were used in an uncalibrated fashion. We analyzed the measured cardiac index using a Bland-Altman analysis (the method of variance estimates recovery), a polar plot method (half-moon method), a 4-quadrant plot and compared the widths of the limits of agreement (LOA) using an F test. One OPCAB patient was excluded because of the use of an intra-aortic balloon pumping during surgery, and 20 patients (10 OPCAB and 10 LDLT) were ultimately analyzed. We obtained 149 triplet measurements with a wide range of cardiac index. For the FloTrac/Vigileo™, the bias and percentage error were -0.44 L/min/m2 and 74.4 %. For the LiDCOrapid™, the bias and percentage error were -0.38 L/min/m2 and 53.5 %. The polar plot method showed an angular bias (FloTrac/Vigileo™ vs. LiDCOrapid™: 6.6° vs. 5.8°, respectively) and radial limits of agreement (-63.9 to 77.1 vs. -41.6 to 53.1). A 4-quadrant plot was used to obtain concordance rates (FloTrac/Vigileo™ vs. PAC and LiDCOrapid™ vs. PAC: 84.0 and 92.4 %, respectively). We could compare CO measurement devices across broad ranges of CO and SVR using LDLT and OPCAB surgical patients. An F test revealed no significant difference in the widths of the LoA for both devices when sample sizes capable of detecting a more than two-fold difference were used. We found that both devices tended to underestimate the calculated CIs when the CIs were relatively high. These proportional bias produced large percentage errors in the present study.

M3muscarinic receptors mediate acetylcholine-induced pulmonary vasodilation in pulmonary hypertension.

Information about the muscarinic receptor subtype(s) mediating pulmonary circulatory vasodilator responses to acetylcholine (ACh) is limited. The aim of this study was to pharmacologically characterize the muscarinic receptors associated with ACh-induced pulmonary vasodilation in a pulmonary hypertension model. Vasodilation of rabbit isolated buffer-perfused lungs in which pulmonary hypertension was induced with the thromboxane A2 analogue U-46619 was evoked by ACh at a just maximally effective concentration (2 x 10⁻7 M). The effects of cumulative concentrations of three specific muscarinic receptor subtype antagonists [pirenzepine (M1), methoctramine (M2), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M3] on ACh-induced pulmonary vasodilation were determined. Double vascular occlusion pressure was recorded to locate the muscarinic receptors within the pulmonary vasculature. Based on the 50% inhibitory concentrations (IC50), the rank of order of antagonist potency was 4-DAMP >> pirenzepine > methoctramine. The vascular effects of all three inhibitors were localized to the precapillary segment. These findings suggest that the vasodilator action of ACh on rabbit isolated perfused U-46619 pretreated lungs is mediated by M3 muscarinic receptors located in the pulmonary arterial bed.

[Second-degree atrioventricular block (Mobitz type II) probably exaggerated by dopamine during anesthetic management for a patient with ochronosis: a case report].

Ochronosis is a rare disease. Usually symptoms appear in the third, fourth, or later decade of life. The most common symptom is arthropathy, but cardiovascular system can be involved in this disease. A 71-year-old man with ochronosis was scheduled for total hip arthroplasty. Preoperatively, echocardiogram revealed aortic valve stenosis, mitral valve stenosis, and hypokinesis on antero-septal, lateral and posterior walls. Coronary angiogram revealed 50-75% stenosis of the left anterior descending coronary artery (segment 7) and 100% stenosis of the left circumflex artery (segment 15). Before the induction of general anesthesia, electrocardiogram showed first-degree atrioventricular block. After the induction of general anesthesia, blood pressure decreased markedly. Phenylephrine administration and rapid infusion of extracellular fluid failed to increase blood pressure. Thus, we started to administer dopamine at an infusion rate of 10 microg x kg(-1) x min(-1) which increased blood pressure effectively, but electrocardiogram showed second-degree atrioventricular block (Mobitz type II). We started rapid infusion of a plasma substitute, and gradually decreased the infusion rate of dopamine to 4 microg x kg(-1) x min(-1). Then electrocardiogram returned to first-degree atrioventricular block. We estimated that second-degree atrioventricular block in this patient might have been exaggerated by dopamine at least in part.

[Anesthetic management of four patients with Fournier syndrome].

We experienced anesthetic managements of four patients with Fournier syndrome. In the anesthetic management of the patients with Fournier syndrome the following three points should be kept in mind; (a) the necessity of careful preoperative examination, (b) the better anesthesia, and (c) the careful postoperative care.

Time course of systolic and diastolic blood pressure decreases during the preintubation period of anesthesia induction: modeling with a logistic function.

STUDY OBJECTIVE: To investigate whether systolic (SBP) and diastolic blood pressure (DBP) decreases during the preintubation period could be expressed as 4-parameter logistic and cubic functions giving S-shaped curves. DESIGN: Prospective, clinical study. SETTING: Operating room of a metropolitan general hospital. PATIENTS: Seven ASA physical status I and II patients scheduled for elective spinal surgery during general anesthesia. INTERVENTIONS: Anesthesia was induced with fentanyl, propofol, and vecuronium injection followed by inhalation of sevoflurane. MEASUREMENTS: The SBP and DBP data were recorded at all beats from fentanyl injection to direct laryngoscopy. The respective changes were analyzed using a logistic function: P(t) = p(L) + (q(L) - p(L))/(1 + exp{[4 m(L)/(q(L) - p(L))][k(L) - t]}) and a cubic function: P(t) = at(3) + bt(2) + ct + d, where parameter p(L) is the upper asymptote, q(L) is the lower asymptote, m(L) is the slope at the inflection point, and k(L) is the time to the inflection point and where a, b, and c are coefficients, and d are constants. Goodness of fit of the two functions was compared using a correlation coefficient and residual mean squares. Each parameter was compared with the corresponding observed data. MAIN RESULTS: Logistic correlation coefficient values for SBP and DBP decreases were larger than the cubic correlation coefficient values (0.990 [Z transformation: 2.64 +/- 0.32] vs 0.981 [Z: 2.32 +/- 0.37] and 0.977 [Z: 2.22 +/- 0.33] vs 0.967 [Z: 2.05 +/- 0.34], respectively; P < 0.05). Logistic residual mean squares values for SBP and DBP decreases were smaller than cubic residual mean squares values (20.6 vs 41.0 and 9.2 vs 13.7 mmHg(2), respectively; P < 0.05). There were significant correlations between p(L) and SBP or DBP after anesthesia induction, between q(L) and SBP or DBP before endotracheal intubation, and between k(L) and time to maximal rate of the SBP or DBP decrease (dP/dt(min)), but no significant correlation between m(L) and dP/dt(min) for SBP or DBP. CONCLUSIONS: Time courses of SBP and DBP decreases during the preintubation period of anesthesia induction are modeled effectively by a logistic function.

[Right bronchial intubation using a left-sided double-lumen tube in a patient with situs inversus].

A 74-year-old man was scheduled for resection of a pulmonary tumor in the left upper lobe. He had asymptomatic complete situs inversus, and therefore his left lung had three lobes whereas his right lung had two. Since the tumor had been growing through the left upper bronchus into the left main bronchus, it seemed that the use of a bronchial blocker in the left bronchus should be avoided. A 37-Fr left-sided double-lumen tube was rotated in the opposite direction (clockwise) and advanced easily into the right (anatomically left) main bronchus under fiberoptic guidance. One lung ventilation during the operation was performed successfully and there was no postoperative airway complication. Several ways of achieving one lung ventilation in patients with situs inversus are discussed in this report. The use of a bronchial blocker should be considered first-choice, but sometimes its use is inappropriate as in this case. Commercially available double-lumen tubes are not intended for use in cases of situs inversus. If a double-lumen tube is desired, intentional right bronchial insertion of a left-sided double-lumen tube seems to be an easy and reliable option.

Intraoperative blood salvage during liver resection: a randomized controlled trial.

OBJECTIVE: A randomized controlled trial was conducted to clarify the effectiveness of intraoperative blood salvage in reducing blood loss. BACKGROUND: Although reduction of central venous pressure (CVP) is thought to decrease blood loss during liver resection, no consistently effective and safe method for obtaining the desired reduction of CVP has been established. METHODS: Living liver donors scheduled to undergo liver graft procurement were randomly assigned to a blood salvage group, in which a blood volume equal to approximately 0.7% of the patient's body weight was collected before the liver transection, or a control group. The surgeons were blinded to the randomization results. The primary outcome measure was blood loss during liver parenchymal division. A multivariate analysis was also performed. RESULTS: Seventy-nine donors were allocated intraoperatively to the blood salvage group (n = 40) or the control group (n = 39). The amount of blood loss during liver transection was significantly smaller in the blood salvage group than in the control group (median loss during transection, 140 mL vs. 230 mL, P = 0.034). The CVP at the beginning of the liver parenchymal division was significantly lower in the blood salvage group than in the control group (median, 5 cm H2O vs. 6 cm H2O, P = 0.005). The results of a multivariate analysis revealed that intraoperative blood salvage offered the advantage of reduced blood loss during liver parenchymal division (adjusted OR, 0.31; 95% CI, 0.11-0.85, P = 0.025). CONCLUSION: Modest intraoperative blood salvage significantly and safely reduced blood loss during hepatic parenchymal transection.

Effects of deep hypothermic circulatory arrest with retrograde cerebral perfusion on electroencephalographic bispectral index and suppression ratio.

OBJECTIVE: No systematic study has been conducted to investigate effects of deep hypothermic circulatory arrest (DHCA) on electroencephalographic bispectral index (BIS) and suppression ratio (SR). Thus, the effects of DHCA were evaluated on BIS and SR. DESIGN: A prospective clinical study. SETTING: University hospital (single institute). PARTICIPANTS: Twenty consecutive patients undergoing thoracic aortic surgery using DHCA under narcotics-sevoflurane anesthesia. INTERVENTIONS: BIS and SR were monitored during cardiopulmonary bypass, simultaneously with nasopharyngeal temperature (NPT). MEASUREMENTS AND MAIN RESULTS: BIS decreased to 0 with induction of deep hypothermia and rose again with rewarming, although rates of BIS changes in response to cooling and rewarming varied widely among patients. Typically, BIS decreased slowly until NPT reached 26 degrees C during cooling and then it began to decrease rapidly and reached 0 at 17 degrees C, in inverse proportion to SR, which increased rapidly with deep hypothermia and reached 100% at 17 degrees C. When SR was 50% or more, BIS was determined by SR according to the expression: BIS = 50-SR/2. With rewarming, BIS rose again and returned to precooling baseline levels. Time to the beginning of the BIS recovery significantly correlated with duration of DHCA. CONCLUSIONS: With induction of deep hypothermia, BIS decreased in a biphasic manner to 0 at rates varying among patients. With rewarming, BIS rose again at rates extremely widely varying among patients. The rate of BIS recovery was related to duration of DHCA. BIS may be capable of conveniently tracing suppression and recovery of a part of cerebral electrical activity before, during, and after DHCA.

Anti-allodynic and anti-hyperalgesic effects of nociceptin receptor antagonist, JTC-801, in rats after spinal nerve injury and inflammation.

The effects of nociceptin/orphanin FQ (N/OFQ) peptide receptor antagonist JTC-801 on allodynia and hyperalgesia were examined in rats in order to explore the involvement of N/OFQ system in these pathological pain states. Tactile allodynia induced by L5/L6 spinal nerve ligation was reversed by both systemic (3-30 mg/kg) and spinal (22.5 and 45 pg) JTC-801 in a dose-dependent manner. Concerning hyperalgesia induced by formalin injection into the hindpaw, JTC-801 dose-dependently suppressed the second phase, but not the first phase, of the licking behavior. Furthermore, systemic JTC-801 reduced Fos-like immunoreactivity in the dorsal horn of the spinal cord (laminae I/II). In conclusion, N/OFQ receptor antagonist JTC-801 exerted anti-allodynic and anti-hyperalgesic effects in rats, suggesting that N/OFQ system might be involved in the modulation of neuropathic pain and inflammatory hyperalgesia.

Brain stem opioidergic and GABAergic neurons mediate the antinociceptive effect of nitrous oxide in Fischer rats.

BACKGROUND: Recent studies have revealed that N2O exerts its antinociceptive effect by inducing opioid peptide release in the brain stem, thereby activating the descending noradrenergic inhibitory neurons, which modulate pain processing in the spinal cord. However, the precise neuronal pathways that mediate these events remain to be determined. METHODS: Using immunohistochemical and behavioral techniques in adult male Fischer rats, the authors studied the involvement of brain stem opioidergic and gamma-aminobutyric acid-mediated (GABAergic) neurons in the N2O-induced antinociceptive effect using discrete microinjections of an opioid receptor antagonist or GABAergic activator into the periaqueductal gray area and pontine noradrenergic nuclei. They used c-Fos expression as an immunohistochemical mark of neuronal activation induced by N2O and the plantar test as the behavioral paradigm for nociception. RESULTS: Microinjection of either naloxone (an opioid receptor antagonist) or muscimol (a gamma-aminobutyric acid receptor type A agonist) into the ventrolateral periaqueductal gray area inhibited N2O-induced c-Fos expression in the spinal cord and pontine noradrenergic nuclei, particularly in the A7. Microinjection of either naloxone or muscimol into the A7 nuclei also inhibited N2O-induced c-Fos expression in the spinal cord and the N2O-induced antinociceptive effect by the plantar test. CONCLUSIONS: These results support the hypothesis that both opioidergic and GABAergic neurons mediate the antinociceptive effect of N2O at the periaqueductal gray area and A7 in the brain stem. The authors postulate that N2O-induced opioid peptide release leads to inhibition of GABAergic neurons via opioid receptors. The descending noradrenergic inhibitory pathways, which are tonically inhibited by these gamma-aminobutyric acid neurons, are thereby activated (disinhibited) and modulate pain processing in the spinal cord.

GABAergic interneurons at supraspinal and spinal levels differentially modulate the antinociceptive effect of nitrous oxide in Fischer rats.

BACKGROUND: The study hypothesizes that nitrous oxide (N(2)O) releases opioid peptide in the brain stem, which results in inhibition of gamma-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of alpha2 adrenoceptor and indirect activation of GABAergic neurons through alpha1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N(2)O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N(2)O-induced antinociceptive effect. METHODS: Adult male Fischer rats were administered muscimol (GABA(A) receptor agonist) intracerebroventricularly (icv), gabazine (GABA(A) receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N(2)O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically. RESULTS: The N(2)O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N(2)O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord. CONCLUSIONS: The GABAergic neurons modulate the antinociceptive effect of N(2)O in opposite directions at supraspinal and spinal levels. The pronociceptive effects of enhancement at the supraspinal GABAergic site predominate in response to systemically administered midazolam.

Evidence for the involvement of spinal cord alpha1 adrenoceptors in nitrous oxide-induced antinociceptive effects in Fischer rats.

BACKGROUND: In a previous study, the authors found that nitrous oxide (N2O) exposure induces c-Fos (an immunohistochemical marker of neuronal activation) in spinal cord gamma-aminobutyric acid-mediated (GABAergic) neurons in Fischer rats. In this study, the authors sought evidence for the involvement of alpha1 adrenoceptors in the antinociceptive effect of N2O and in activation of GABAergic neurons in the spinal cord. METHODS: Adult male Fischer rats were injected intraperitoneally with alpha1 adrenoceptor antagonist, alpha2 adrenoceptor antagonist, opioid receptor antagonist, or serotonin receptor antagonist and, 15 min later, were exposed to either air (control) or 75% N2O. In some animals, nociception was investigated with the plantar test after 30 min of exposure, while in other animals, gas exposure was continued for 90 min and the spinal cord was examined for c-Fos immunostaining. In a separate experiment, animals were exposed to the above gases alone, after which the spinal cords were examined immunohistochemically for c-Fos and alpha1 adrenoceptor by double-staining methods. RESULTS: The antinociceptive effect of N2O was attenuated by prazosin (an alpha1 adrenoceptor antagonist), yohimbine (an alpha2 adrenoceptor antagonist), and naloxone (an opioid receptor antagonist) but not by methysergide and tropisetron (serotonin receptor antagonists). N2O exposure induced c-Fos expression in the spinal cord, which was blocked by prazosin and naloxone but not by other drugs. N2O-induced c-Fos expression was colocalized with alpha1 adrenoceptor immunoreactivity in laminae III-IV. CONCLUSIONS: These findings support the hypothesis that N2O activates GABAergic interneurons through alpha1 adrenoceptors to produce its antinociceptive effect.

Effect of hypoventilation on bleeding during hepatic resection: a randomized controlled trial.

HYPOTHESIS: Blood loss in hepatic resection is an important determinant of operative outcome. OBJECTIVE: To clarify whether reducing the tidal volume would be effective in decreasing blood loss during liver transection. DESIGN: Randomized controlled trial. SETTING: University hospital. PATIENTS: Eighty patients scheduled to undergo hepatic resection were randomly assigned to receive liver transection under normoventilation (n = 40) or hypoventilation (n = 40). INTERVENTIONS: During liver transection, in the normoventilation group, the tidal volume was 10 mL/kg and the respiratory rate was 10/min; in the hypoventilation group, the tidal volume was reduced to 4 mL/kg and respiratory rate was increased to 15/min. Liver transection was performed under total or selective inflow occlusion. MAIN OUTCOME MEASURE: Blood loss. RESULTS: Between the normoventilation and hypoventilation groups, no significant difference was found in total blood loss (median [range]: 630 mL [72-3600 mL] vs 630 mL [120-3520 mL]; P =.44) or blood loss per transection area (median [range]: 7.3 mL/cm(2) [1.2-55.4 mL/cm(2)] vs 9.8 mL/cm(2) [0.9-79.9 mL/cm(2)]; P =.55). During liver transection, the central venous pressure was significantly reduced in the hypoventilation group than in the normoventilation group (median [range]: -0.7 cm H(2)O [-3.0 to 1.8 cm H(2)O] vs -0.2 cm H(2)O [-4.0 to 2.0 cm H(2)O]; P =.007). The maximum end-tidal carbon dioxide level in the hypoventilation group was significantly higher than that in the normoventilation group (maximum [range]: 50 mm Hg [28-66 mm Hg] vs 37 mm Hg [27-60 mm Hg]; P<.001). Transection time, postoperative liver function, hospitalization length, morbidity, and mortality were similar in the 2 groups. CONCLUSION: This randomized trial suggested no beneficial effect of reduction of tidal volume on bleeding during hepatic resection.