Effect of fibrinogen replacement therapy on bleeding outcomes and 1-year mortality in patients undergoing thoracic aortic surgery: a retrospective cohort study.

PURPOSE: This study aimed to examine the effect of fibrinogen replacement therapy with cryoprecipitate or fibrinogen concentrate on bleeding outcomes and 1-year mortality in patients undergoing thoracic aortic surgery. METHODS: We retrospectively studied 439 consecutive patients who underwent thoracic aortic surgery with cardiopulmonary bypass between January 1st, 2010 and December 31st, 2019 and identified patients who received cryoprecipitate or fibrinogen concentrate (the fibrinogen replacement group) and those who did not (the control group). Multivariate analyses were performed to examine the associations of fibrinogen replacement therapy with perioperative major bleeding (i.e., excessive hemorrhage or blood transfusion), re-exploration for bleeding, and 1-year mortality. RESULTS: There were 285 patients in the fibrinogen replacement group who received 2.2 ± 1.0 g of concentrated fibrinogen amount and 154 patients in the control group. The incidence of major bleeding in the fibrinogen replacement group was less than that in the control group in patients with fibrinogen level < 150 mg/dL during cardiopulmonary bypass (49.7% versus 74.6%, p = 0.0007, multivariate odds ratio; 0.33, 95% confidence intervals; 0.12-0.91, p = 0.03), but not in patients with fibrinogen level ≥ 150 mg/dL (25.0% versus 29.6%, p = 0.51). No significant difference was found in re-exploration for bleeding (1.0% versus 1.3%, p = 1.00) or 1-year mortality (10.4% versus 5.3%, multivariate Cox proportional-hazard ratio; 1.03, 95% confidence intervals; 0.82-1.31, p = 0.74) between the fibrinogen replacement group and the control group. CONCLUSIONS: The results of this study indicate that 2-3 g of fibrinogen replacement reduces the incidence of major bleeding in patients with hypofibrinogenemia during cardiopulmonary bypass in thoracic aortic surgery.

Restrictive blood transfusion and 1-year mortality in patients undergoing open abdominal surgery: A retrospective propensity score-matched cohort study.

BACKGROUND: The importance of patient blood management is increasingly recognized in surgery patients. This study aimed to examine the effect of perioperative restrictive blood transfusion on 1-year mortality and blood transfusion rate in open abdominal surgery. METHODS: We retrospectively studied 452 consecutive patients who underwent open abdominal surgery before (liberal group: 233 patients) and after (restrictive group: 219 patients) implementing intraoperative restrictive transfusion of red blood cell. The trigger levels of hemoglobin were less than 9-10 g/dL in the liberal group and less than 7-8 g/dL in the restrictive group. All-cause mortality at 1-year as the primary outcome and the transfusion rate of any allogeneic blood products as secondary outcome were compared between the liberal group and the restrictive group by the propensity-score matching. RESULTS: Among a total of 452 patients (69 ± 11 yr., 70.5 % men), overall mortality at 1 year was 8.4 % and the proportion of patients who received any allogeneic blood products was 19.6 %. Compared with 155 propensity-score matched patients of the liberal group, 155 matched patients of the restrictive group had significantly lower 1-year mortality (4 [2.5 %] versus 18 [11.6 %], p = 0.003, percent absolute risk reduction [%ARR]; 9.0, 95 % confidential interval [CI], 3.1-14.7) and had significantly lower proportion of patients who received any allogeneic blood products (21 [13.5 %] versus 41 [26.4 %], p = 0.006, %ARR; 12.9, 95 % CI, 3.9-21.5). CONCLUSIONS: The results of this study indicate that intraoperative restrictive blood transfusion reduces 1-year mortality and the transfusion rate of allogeneic blood products.

Effect of an assessment of fibrin-based rotational thromboelastometry on blood transfusion and clinical outcomes in cardiovascular surgery: A cohort study.

The clinical importance of viscoelastic testing in patient blood management when performing cardiovascular surgery is increasing. We aimed to examine the effect of a blood transfusion protocol including an assessment of fibrin-based rotational thromboelastometry on transfusion volume, mortality, and bleeding complications in patients undergoing cardiac or thoracic aortic surgery. We retrospectively studied a cohort of 376 consecutive patients who underwent cardiopulmonary bypass before (control group: 150 cardiac and 35 thoracic aortic surgeries) and after (assessment group: 154 cardiac and 37 thoracic aortic surgeries) introducing the fibrin polymerization assessment with thromboelastometry in the blood transfusion protocol. The transfusion volume and clinical outcomes were compared between the control and assessment groups, and the standardized (mean) difference (S[M]D) was calculated as an indicator of statistical effect size. Compared with the control group, the assessment group had a lower total blood transfusion volume (mL) in cardiac (2720 ± 1282 vs. 2034 ± 1330, p < 0.0001, [SMD] = 0.68) and thoracic aortic surgeries (5236 ± 2732 vs. 3714 ± 1768, p < 0.0001, SMD = 0.67). The 1-year mortality rates were 1.9 % and 2.7 % in cardiac and thoracic aortic surgeries, respectively. Significant differences were not observed in the 1-year mortality (3.2 % vs. 1.0 %, p = 0.16, relative risk [RR] = 0.32 with 95 % confidence intervals [CI] = 0.06-1.57, SD = 0.15), re-exploration for bleeding (4.8 % vs. 2.6 %, p = 0.28, RR = 0.53 with 95 % CI = 0.18-1.57, SD = 0.12), and major bleeding (17.3 % vs. 13.0 %, p = 0.31, RR = 0.75 with 95 % CI = 0.46-1.22, SD = 0.12) rates between the control and assessment groups. The assessment of fibrin polymerization with thromboelastometry using the blood transfusion protocol reduced the blood transfusion volume in cardiovascular surgery.

Clinical Simulation Model of Fibrinogen Decline During Hemorrhage in Major Noncardiac Surgery.

BACKGROUND: Monitoring of decrease in fibrinogen levels with surgical blood loss is crucial for timely transfusion of fresh frozen plasma (FFP) to avoid coagulopathic bleeding. Here, we validated a simulation model to predict hemorrhagic reductions in fibrinogen levels during major noncardiac surgery. METHODS: We retrospectively performed exponential regression analysis of intraoperative blood loss and fibrinogen levels to develop a simulation model in the initial 50 patients and applied the model to another 59 patients to compare the measured and simulated fibrinogen levels. We examined the relationship between FFP transfusion and the measured fibrinogen levels or blood loss. The fibrinogen trigger level of FFP transfusion was below 130 mg/dL, although the decision of a perioperative blood transfusion was at the discretion of the anesthesiologists and surgeons. RESULTS: Application of the simulation model based on the initial 50 patients to another 59 patients showed no difference between the measured and estimated fibrinogen levels (189 ± 61 versus 186 ± 62, P = 0.60, mean difference: -2.28, limits of agreement: -69.42 to 64.84). The estimated fibrinogen level (mg/dL) = preoperative fibrinogen × exp (-1.90 × [blood loss/estimated circulation volume]), in which the estimated circulation volume = (70 [mL/kg] × body weight [kg]). FFP transfusion was significantly related to the measured fibrinogen level (cutoff: 145; 95% confidence intervals: 124-168; P = 0.0003) but not blood loss (P = 0.12). CONCLUSIONS: Fibrinogen level simulation predicted a hemorrhagic fibrinogen decline, thereby guiding FFP transfusion during active surgical bleeding. Further studies on the usefulness of fibrinogen level simulation are warranted.

Allergic Acute Coronary Artery Stent Thrombosis After the Administration of Sugammadex in a Patient Undergoing General Anesthesia: A Case Report.

In addition to cutaneous, gastrointestinal, hemodynamic, and respiratory symptoms, allergic reactions can induce an acute coronary syndrome in normal or atheromatous coronary arteries and can cause coronary stent thrombosis. Here, we report a case of coronary stent thrombosis due to allergic acute coronary syndrome during anaphylaxis induced by sugammadex in a female patient undergoing general anesthesia. She was emergently treated with percutaneous transluminal coronary balloon angioplasty with catecholamine, vasodilator, and intraaortic balloon support. Knowledge of perioperative allergy-triggered acute coronary syndrome is crucial for prompt and appropriate treatment.

Effect of Furosemide under Hyperchloremic Acidosis on Intraoperative Oliguria and Acute Kidney Injury in Patients with Normal Renal Function.

BACKGROUND: Renal function tends to deteriorate in a hyperchloremic acidifying environment, which is reflected by a decrease in the difference between sodium and chloride. OBJECTIVES: To examine the effect of furosemide administered under hyperchloremic acidosis on intraoperative oliguria and acute kidney injury in patients with preoperatively normal renal function. METHODS: In patients undergoing abdominal or orthopedic surgeries (April 2010-November 2018), we retrospectively identified patients who preoperatively had a normal renal function but experienced intraoperative oliguria under hyperchloremic acidosis (a sodium-chloride difference < 30 mEq/L) without dehydration. We compared the perioperative urine output and the incidence of postoperative acute kidney injury between patients who intraoperatively received an initial dose of 5 mg of furosemide (the furosemide group) and patients who did not intraoperatively receive furosemide (the control group). RESULTS: We identified 62 patients in the furosemide group and 48 patients in the control group. The furosemide group intraoperatively received 0.11 ± 0.06 mg/kg of furosemide (range 0.06-0.39 mg/kg). Compared to the control group, the furosemide group had greater urine output (mL/kg/h) in the operating room (1.1 ± 0.7 vs. 0.3 ± 0.1, p < 0.01) and on postoperative day 1 (1.2 ± 0.5 vs. 1.1 ± 0.4, p = 0.02). The incidence of postoperative acute kidney injury was lesser in the furosemide group than that in the control group (8.0 vs. 27.0%, p < 0.01; multivariate OR 0.18; 95% CI 0.05-0.61; p < 0.01). CONCLUSIONS: In surgery patients under hyperchloremic acidosis, furosemide (0.1 mg/kg) resolved intraoperative oliguria and reduced the incidence of postoperative acute kidney injury.

[A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after Selection of an Alternative Drug after a Skin Test].

We report our experience of a patient with a history of anaphylactic shock suspected to be caused by rocuronium who was scheduled to undergo hepatic tumor resection. The patient was a 17-year-old female (height : 166 cm, weight : 46 kg). During general anesthesia at another hospital several years ago, she had an anaphylactic shock, and rocuronium was suspected to be the offending drug. To collect information and search for the cause, skin tests were performed for rocuronium, vecuronium and suxamethonium. She was positive for rocuronium, and negative for other drugs. At anesthesia induction, we administered vecuronium and confirmed no development of anaphylaxis before commencement of surgery. In the perioperative period, she had no symptoms that indicated anaphylaxis. Since there is potential high cross-reactivity among muscle relaxants, it is important to perform a test for alternative drugs when a muscle relaxant may be a cause of anaphylaxis. Selection and administration of an alternative drug should be carefully performed, even when a skin test is negative for the alternative drug.

Influence of progressive hemorrhage and subsequent cardiopulmonary resuscitation on the bispectral index during isoflurane anesthesia in a swine model.

BACKGROUND: The bispectral index for measurement of anesthetic depth may be modified by extreme hypotension during hemorrhagic shock. In this study, the influence of progressive hemorrhage and subsequent cardiopulmonary resuscitation on the bispectral index was investigated under controlled anesthetic depth. METHODS: Fifteen swine were anesthetized through inhalation of isoflurane under bispectral index monitoring. Hemorrhagic shock was induced using a stepwise hemorrhage model in which 20%, 10%, and 10% of estimated blood volume were removed over three 30-minute periods and then 5% was removed every 30 minutes until the mean arterial pressure was less than 10 mm Hg. After reaching this criterion, chest compression with 0.2-mg/kg epinephrine and hydroxyethyl starch infusion was performed for 20 minutes or until the mean arterial pressure exceeded 50 mm Hg. The pharmacodynamics of the isoflurane effect was examined before hemorrhage, after 40% bleeding, and after resuscitation. RESULTS: A mean (SD) volume of 836 (78) mL of blood was drained before resuscitation. The bispectral index suddenly decreased at a mean (SD) arterial pressure of 22 (3) mm Hg and showed isoelectric activity in most animals before resuscitation. Eight pigs were resuscitated, and the bispectral index recovered during a range of periods after recovery of the mean arterial pressure. The pharmacodynamic effect of isoflurane did not change after 40% bleeding but increased after resuscitation, with the alteration correlated with the time for resuscitation. CONCLUSION: In hemorrhagic shock, the bispectral index merely reflects the anesthetic depth until development of lethal hypotension at which brain electrical activity cannot be sustained. After recovery from depression, the potency of isoflurane can increase depending on the cerebral hypoperfusion time. The increased bispectral index for anesthetics after resuscitation might reflect the degree of cerebral damage due to hypoperfusion.

Deterioration of myocardial injury due to dexmedetomidine administration after myocardial ischaemia.

AIM: Dexmedetomidine is a highly selective α-2 adrenergic agonist used perioperatively. Dexmedetomidine's cardioprotective effect after myocardial ischaemia remains unknown. In this study, we administered dexmedetomidine after ischaemia to investigate its ability to protect the cardiac muscle from ischaemia-reperfusion injury in isolated rat hearts. METHODS: After a 30-min stop of perfusion, isolated rat hearts underwent reperfusion for 120 min. At the initiation of reperfusion, dexmedetomidine was administered for 25 min at concentrations of 0 nM (control group), 1 nM (Dex 1 group), and 10 nM (Dex 10 group). Yohimbine (an α-2 adrenergic antagonist) was administered in the manner as above in another group of isolated rat hearts at a concentration of 1 µM without dexmedetomidine (Yoh group) and at 1 µM with 10 nM dexmedetomidine (Yoh+Dex 10 group). The area of infarction was measured using 2,3,5-triphenyltetrazolium staining. RESULTS: Dexmedetomidine administration did not influence haemodynamics or the coronary flow (CF), but did increase the myocardial infarct size. Neither concentration of dexmedetomidine affected the infarct size as the Dex 1 and Dex 10 groups had almost the same infarct size. The infarct size was 40.5±2.9% in the control group, 60.9±5.3% in the Dex 1 group, and 60.9±2.8% in the Dex 10 group. The infarct size was reduced in the yohimbine groups. The infarct size was 39.2±3.3% in the Yoh+Dex 10 group and 45.0±3.2% in the Yoh group. CONCLUSION: Dexmedetomidine administration does not influence haemodynamics or CF, but does increase the cardiac infarct size. α-2 Adrenergic stimulation may induce this mechanism.

The influence of endotoxemia on the electroencephalographic and antinociceptive effects of isoflurane in a swine model.

BACKGROUND: We have previously reported that hemorrhagic shock decreases the minimum alveolar anesthetic concentration (MAC) of isoflurane but minimally alters the electroencephalographic (EEG) effect. In this study, we investigated the influence of endotoxemia on the EEG effect and the MAC of isoflurane. METHODS: Eighteen swine (25.7 +/- 2.3 kg) were anesthetized by inhalation of isoflurane. The inhaled concentration was decreased to 0.5% and maintained for 20 min, before being returned to 2% and maintained for a further 20 min. End-tidal isoflurane concentrations and spectral edge frequencies were recorded. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for spectral edge frequencies versus effect-site concentration. After measurement of the EEG effect, MAC was determined using the dewclaw clamp technique in which movement in response to clamping is recorded. After completion of control measurements, infusion of lipopolysaccharide (LPS, 1 microg x kg(-1) x h(-1)) was started after a 100-microg bolus administration. After 1 h, the inhaled concentration of isoflurane was varied as in the control period, and the MAC was assessed again (LPS1h). The same procedures were also performed after 3 h of LPS infusion (LPS3h). RESULTS: Endotoxemia decreased the effect-site concentration that produced 50% of the maximal effect from 1.31% +/- 0.22% to 1.13% +/- 0.14% (LPS1h) and 1.03% +/- 0.22% (LPS3h) and decreased the MAC from 2.05% +/- 0.20% to 1.51% +/- 0.30% (LPS1h) and 1.21% +/- 0.29% (LPS3h). CONCLUSIONS: Endotoxemia increases both the hypnotic and antinociceptive effects of isoflurane, in contrast to hemorrhagic shock, and the extent of these alterations increases with progression of endotoxemia.

Landiolol, an ultra short acting beta1-blocker, improves pulmonary edema after cardiopulmonary resuscitation with epinephrine in rats.

PURPOSE: Epinephrine is frequently administered as an essential drug for cardiopulmonary resuscitation (CPR) in clinical situations. Unfortunately, epinephrine elicits unfavorable effects, for example pulmonary edema, both during and after CPR. We hypothesized that administration of landiolol during CPR with epinephrine would reduce the degree of pulmonary edema and improve survival. Therefore using a rat CPR model, we investigated the effect of landiolol with epinephrine on pulmonary and cardiac injury following CPR. METHODS: Twelve male Sprague-Dawley rats were allocated to Group-E (Gr.-E: 0.02 mg/kg epinephrine) and thirteen animals to Group-EL (Gr.-EL: 0.02 mg/kg epinephrine with 0.5 mg/kg landiolol). After tracheotomy, cardiac arrest was induced by obstructing the endotracheal tube. We measured the lung wet-to-dry (W/D) weight ratio to evaluate the degree of pulmonary edema 2 h after CPR. The hematocrit (Hct) difference between before and after CPR (Hct-D) was calculated. We measured the plasma levels of troponin-I (T-I) to evaluate the degree of cardiac injury. RESULTS: The lung W/D weight ratio in Gr.-E (6.4 +/- 1.06, mean +/- SD) was significantly higher than that for Gr.-EL (4.9 +/- 0.80, p < 0.01). Hct-D was significantly higher in Gr.-E (10.2 +/- 3.1%) than in Gr.-EL (5.2 +/- 3.5%, p < 0.01). We observed no difference in survival or difference of T-I. (Gr.-E: 2.62 +/- 0.51 ng/ml, Gr.-EL: 3.43 +/- 2.72 ng/ml). CONCLUSION: Administration of landiolol during CPR with epinephrine prevented the development of pulmonary edema and the increase in Hct during and after CPR.

The influence of hemorrhagic shock on the electroencephalographic and immobilizing effects of propofol in a swine model.

BACKGROUND: Hemorrhagic shock increases the hypnotic effect of propofol, but the influence of hemorrhagic shock on the immobilizing effect of propofol is not fully defined. METHODS: Twenty-four swine (30.3 +/- 3.6 kg) were anesthetized by inhalation of isoflurane and randomly assigned to either a control (n = 12) or a hemorrhagic shock (n = 12) group. Animals in the shock group were bled to a mean arterial blood pressure of 50 mm Hg and maintained at this level for 60 min. After isoflurane inhalation was stopped, propofol was infused at 50 mg x kg(-1) x h(-1) until no movement was observed after application of a dewclaw clamp every 2 min. Arterial samples for measurement of the propofol concentration were collected just before each use of the dewclaw clamp and the Bispectral Index (BIS) was also recorded. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for BIS versus effect-site concentration and a logistic regression analysis for the probability of movement versus effect-site concentration. RESULTS: The propofol doses needed to reach a 50% decrease from baseline BIS, and no movement after noxious stimuli were reduced by hemorrhagic shock by 54% and 38%, respectively. Hemorrhagic shock decreased the effect-site concentration that produced 50% of the maximal BIS effect from 11.6 +/- 3.8 to 9.1 +/- 1.7 microg/mL and that producing a 50% probability of movement from 26.8 +/- 1.0 to 20.6 +/- 1.0 microg/mL. CONCLUSIONS: The results show that hemorrhagic shock increases both the hypnotic and immobilizing effects of propofol due to pharmacokinetic and pharmacodynamic alterations, with the changes in pharmacodynamics occurring to a similar extent for both effects.

The influence of hemorrhagic shock on the minimum alveolar anesthetic concentration of isoflurane in a swine model.

BACKGROUND: Although hemorrhagic shock decreases the minimum alveolar concentration (MAC) of inhaled anesthetics, it minimally alters the electroencephalographic (EEG) effect. Hemorrhagic shock also induces the release of endorphins, which are naturally occurring opioids. We tested whether the release of such opioids might explain the decrease in MAC. METHODS: Using the dew claw-clamp technique in 11 swine, we determined the isoflurane MAC before hemorrhage, after removal of 30% of the estimated blood volume (21 mL/kg of blood over 30 min), after fluid resuscitation using a volume of hydroxyethylstarch equivalent to the blood withdrawn, and after IV administration of 0.1 mg/kg of the mu-opioid antagonist naloxone. RESULTS: Hemorrhagic shock decreased the isoflurane MAC from 2.05% +/- 0.28% to 1.50% +/- 0.51% (P = 0.0007). Fluid resuscitation did not reverse MAC (1.59% +/- 0.53%), but additional administration of naloxone restored it to control levels (1.96% +/- 0.26%). The MAC values decreased depending on the severity of the shock, but the alterations in hemodynamic variables and metabolic changes accompanying fluid resuscitation or naloxone administration did not explain the changes in MAC. CONCLUSIONS: Consistent with previous reports, we found that hemorrhagic shock decreases MAC. In addition, we found that naloxone administration reversed the effect on MAC, and we propose that activation of the endogenous opioid system accounts for the decrease in MAC during hemorrhagic shock. Such an activation would not be expected to materially alter the EEG, an expectation consistent with our previous finding that hemorrhagic shock minimally alters the EEG.

Landiolol, an ultra short-acting beta1-adrenoceptor antagonist, does not alter the minimum alveolar anesthetic concentration of isoflurane in a swine model.

BACKGROUND: We previously reported that landiolol, an ultra-short-acting beta1-adrenoceptor antagonist, does not alter the electroencephalographic effect of isoflurane. Here, we investigated the influence of landiolol on the minimum alveolar anesthetic concentration (MAC) of isoflurane required to prevent movement in response to a noxious stimulus in 50% of subjects. METHODS: Ten swine (29.0 +/- 3.4 kg) were anesthetized by inhalation of isoflurane. MAC was determined using the dewclaw clamp technique, in which movement in response to clamping is recorded. After determination of MAC in the baseline period, an infusion of landiolol (0.125 mg x kg(-1) x min(-1) for 1 min, then 0.04 mg x kg(-1) x min(-1)) was started. After a 20-min stabilization period, MAC was again assessed (0.04 mg x kg(-1) x min(-1) landiolol). The infusion of landiolol was then increased from 0.04 to 0.2 mg x kg(-1) x min(-1), and after a 20-min stabilization period, MAC was again assessed (0.2 mg x kg(-1) x min(-1) landiolol). Finally, the infusion of landiolol was stopped, and after a 20-min stabilization period, MAC was assessed for a fourth time (Baseline 2). RESULTS: Landiolol clearly attenuated the increases in heart rate and mean arterial blood pressure that occurred in response to the dewclaw clamp, but did not alter the MAC of isoflurane. CONCLUSIONS: Landiolol does not alter the antinociceptive effect of isoflurane. This result, combined with that from our previous work, also suggests that landiolol does not influence the anesthetic potency of inhaled anesthetics.

Influence of hemorrhagic shock and subsequent fluid resuscitation on the electroencephalographic effect of isoflurane in a swine model.

BACKGROUND: The authors have previously reported that hemorrhage does not alter the electroencephalographic effect of isoflurane under conditions of compensated hemorrhagic shock. Here, they have investigated the influence of decompensated hemorrhagic shock and subsequent fluid resuscitation on the electroencephalographic effect of isoflurane. METHODS: Twelve swine were anesthetized through inhalation of 2% isoflurane. The inhalational concentration was then decreased to 0.5% and maintained for 25 min, before being returned to 2% and maintained for 25 min (control period). Hemorrhagic shock was then induced by removing 28 ml/kg blood over 30 min. After a 30-min stabilization period, the inhalational concentration was varied as in the control period. Finally, fluid infusion was performed over 30 min using a volume of hydroxyethyl starch equivalent to the blood withdrawn. After a 30-min stabilization period, the inhalational concentration was again varied as in the control period. End-tidal isoflurane concentrations and spectral edge frequency were recorded throughout the study. The pharmacodynamics were characterized using a sigmoidal inhibitory maximal effect model for spectral edge frequency versus effect site concentration. RESULTS: Decompensated hemorrhagic shock slightly but significantly shifted the concentration-effect relation to the left, demonstrating a 1.12-fold decrease in the effect site concentration required to achieve 50% of the maximal effect in the spectral edge frequency. Fluid resuscitation reversed the onset of isoflurane, which was delayed by hemorrhage, but did not reverse the increase in end-organ sensitivity. CONCLUSIONS: Although decompensated hemorrhagic shock altered the electroencephalographic effect of isoflurane regardless of fluid resuscitation, the change seemed to be minimal, in contrast to several intravenous anesthetics.

Influence of hypovolemia on the electroencephalographic effect of isoflurane in a swine model.

BACKGROUND: Hypovolemia alters the effect of several intravenous anesthetics by influencing pharmacokinetics and end-organ sensitivity. The authors investigated the influence of hypovolemia on the effect of an inhalation anesthetic, isoflurane, in a swine hemorrhage model. METHODS: Eleven swine were studied. After animal preparation with inhalation of 2% isoflurane anesthesia, the inhalation concentration was decreased to 0.5% and maintained at this level for 25 min before being returned to 2% (control). After 25 min, hypovolemia was induced by removing 14 ml/kg of the initial blood volume via an arterial catheter. After a 25-min stabilization period, the inhalation concentration was decreased to 0.5%, maintained at this level for 25 min, and then returned to 2% (20% bleeding). After another 25 min, a further 7 ml/kg blood was collected, and the inhalation concentration was altered as before (30% bleeding). End-tidal isoflurane concentrations and an electroencephalogram were recorded throughout the study. Spectral edge frequency was used as a measure of the isoflurane effect, and pharmacodynamics were characterized using a sigmoidal inhibitory maximal effect model for the spectral edge frequency versus end-tidal concentration. RESULTS: There was no significant difference in the effect of isoflurane among the conditions used. Hypovolemia did not shift the concentration-effect relation (the effect site concentration that produced 50% of the maximal effect was 1.2 +/- 0.2% under control conditions, 1.2 +/- 0.2% with 20% bleeding, and 1.1 +/- 0.2% with 30% bleeding). CONCLUSIONS: Hypovolemia does not alter the electroencephalographic effect of isoflurane, in contrast to several intravenous anesthetics.

Influence of fluid infusion associated with high-volume blood loss on plasma propofol concentrations.

BACKGROUND: It is common clinical practice to use fluid infusion to manage high-volume blood loss until a blood transfusion is performed. The authors investigated the influence of fluid infusion associated with blood loss on the pseudo-steady state propofol concentration. METHODS: Twenty-seven swine were assigned to a lactated Ringer's solution group, a hydroxyethyl starch group, or a threefold lactated Ringer's solution group (n = 9 in each group). After 180 min of steady state infusion of propofol at a rate of 2 mg.kg(-1).h(-1), hemorrhage and infusion were induced by stepwise bleeding followed by fluid infusion every 30 min. In each of the first two steps, 400 ml blood was collected; thereafter, 200 ml was collected at each step. Just after each bleeding step, fluid infusion was rapidly performed using a volume of lactated Ringer's solution or hydroxyethyl starch equivalent to the blood withdrawn, or a threefold volume of lactated Ringer's solution. Hemodynamic parameters and the plasma propofol concentration were recorded at each step. RESULTS: Although the plasma propofol concentration in the lactated Ringer's solution group increased with hemorrhage and infusion, it decreased in both the hydroxyethyl starch and the threefold lactated Ringer's solution groups. The propofol concentration in the hydroxyethyl starch group could be expressed by the following equation: Plasma Propofol Concentration Decrease (%) = 0.80 x Hematocrit Decrease (%) (r2 = 0.83, P < 0.0001). CONCLUSIONS: When high-volume blood loss is managed by isovolemic hemodilution, the plasma propofol concentration during continuous propofol infusion decreases linearly with the hematocrit decrease.