Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety.

The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a "should be considered" recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure.

Renal effects of norepinephrine-induced variations in mean arterial pressure after liver transplantation: A randomized cross-over trial.

BACKGROUND: Acute kidney injury is commonly seen after liver transplantation. The optimal perioperative target mean arterial pressure (MAP) for renal filtration, perfusion and oxygenation in liver recipients is not known. The effects of norepinephrine-induced changes in MAP on renal blood flow (RBF), oxygen delivery (RDO2 ), glomerular filtration rate (GFR) and renal oxygenation (=renal oxygen extraction, RO2 Ex) were therefore studied early after liver transplantation. METHODS: Ten patients with an intra- and post-operative vasopressor-dependent systemic vasodilation were studied early after liver transplantation during sedation and mechanical ventilation. To achieve target MAP levels of 60, 75 and 90 mm Hg, the norepinephrine infusion rate was randomly and sequentially titrated. At each target MAP, data on cardiac index (CI), RBF and GFR were obtained by transpulmonary thermodilution (PiCCO), the renal vein thermodilution technique and renal extraction of chromium ethylenediaminetetraaceticacid (51 Cr-EDTA), respectively. Renal oxygen consumption (RVO2 ) and extraction (RO2 Ex) were calculated according to standard formulas. RESULTS: At a target MAP of 75 mm Hg, CI (13%), RBF (18%), RDO2 (24%), GFR (31%) and RVO2 (20%) were higher while RO2 Ex was unchanged compared to a target MAP of 60 mm Hg. Increasing MAP from 75 up to 90 mm Hg increased RVR by 38% but had no further effects on CI, RBF, RDO2 or GFR. CONCLUSIONS: In patients undergoing liver transplantation, RBF and GFR are pressure-dependent at MAP levels below 75 mm Hg. Our results suggest that MAP should probably be targeted to approximately 75 mm Hg for optimal perioperative renal filtration, perfusion and oxygenation in patients undergoing liver transplantation.

Inotropic and lusitropic effects of levosimendan and milrinone assessed by strain echocardiography-A randomised trial.

BACKGROUND: We compared the direct inotropic and lusitropic effects of two inodilators, milrinone and levosimendan in patients after aortic valve replacement for aortic stenosis. METHODS: In this randomised, blinded study, 31 patients with normal LV function, were randomised to either levosimendan (0.1 and 0.2 µg/kg/min, n = 15) or milrinone (0.4 and 0.8 µg/kg/min, n = 16) after aortic valve replacement. The effects on LV performance, LV strain, systolic (SR-S) and early diastolic (SR-E) strain rate were assessed by a pulmonary artery catheter and transoesophageal two-dimensional speckle tracking echocardiography of the LV inferior wall. To circumvent the inodilator-induced hemodynamic changes on LV systolic and diastolic deformation, central venous pressure (CVP), systolic artery pressure (SAP), and heart rate were maintained constant by colloid infusion, phenylephrine-induced vasoconstriction and atrial pacing, respectively, during drug infusion. RESULTS: Both inotropic agents induced a dose-dependent increase in cardiac index and stroke volume index by approximately 20% at the highest infusion rates with no differences between groups (P = .139 and .249, respectively). CVP, pulmonary capillary wedge pressure, SAP and heart rate were maintained constant in both groups. LV strain and SR-S increased with both agents, dose-dependently, by 17%-18% and 25%-30%, respectively, at the highest infusion rates, with no difference between groups (P = .434 and .284, respectively). Both agents improved early LV relaxation with no differences between groups (P = .637). At the higher doses, both agents increased SR-E by 30%. CONCLUSIONS: At clinically relevant infusion rates and a certain increase in LV performance the direct inotropic and lusitropic of milrinone and levosimendan were comparable.

Isocapnic hyperventilation provides early extubation after head and neck surgery: A prospective randomized trial.

BACKGROUND: Isocapnic hyperventilation (IHV) shortens recovery time after inhalation anaesthesia by increasing ventilation while maintaining a normal airway carbon dioxide (CO2 )-level. One way of performing IHV is to infuse CO2 to the inspiratory limb of a breathing circuit during mechanical hyperventilation (HV). In a prospective randomized study, we compared this IHV technique to a standard emergence procedure (control). METHODS: Thirty-one adult ASA I-III patients undergoing long-duration (>3 hours) sevoflurane anaesthesia for major head and neck surgery were included and randomized to IHV-treatment (n = 16) or control (n = 15). IHV was performed at minute ventilation 13.6 ± 4.3 L/min and CO2 delivery, dosed according to a nomogram tested in a pilot study. Time to extubation and eye-opening was recorded. Inspired (FICO2 ) and expired (FETCO2 ) CO2 and arterial CO2 levels (PaCO2 ) were monitored. Cognition was tested preoperatively and at 20, 40 and 60 minutes after surgery. RESULTS: Time from turning off the vapourizer to extubation was 13.7 ± 2.5 minutes in the IHV group and 27.4 ± 6.5 minutes in controls (P < .001). Two minutes after extubation, PaCO2 was 6.2 ± 0.5 and 6.2 ± 0.6 kPa in the IHV and control group respectively. In 69% (IHV) vs 53% (controls), post-operative cognition returned to pre-operative values within 40 minutes after surgery (NS). Incidences of pain and nausea/vomiting did not differ between groups. CONCLUSIONS: In this randomized trial comparing an IHV method with a standard weaning procedure, time to extubation was reduced with 50% in the IHV group. The described IHV method can be used to decrease emergence time from inhalation anaesthesia.

Vasopressin and nitroglycerin decrease portal and hepatic venous pressure and hepato-splanchnic blood flow.

BACKGROUND: Various methods are used to reduce venous blood pressure in the hepato-splanchnic circulation, and hence minimise blood loss during liver surgery. Previous studies show that combination of vasopressin and nitroglycerin reduces portal pressure and flow in patients with portal hypertension, and in this study we investigated this combination in patients with normal portal pressure. METHOD: In all, 13 patients were studied. Measurements were made twice to confirm baseline (C1 and BL), during vasopressin infusion 4.8 U/h (V), and during vasopressin infusion combined with nitroglycerin infusion (V + N). Portal venous pressure (PVP), hepatic venous pressure (HVP), central haemodynamics and arterial and venous blood gases were obtained at each measuring point, and portal (splanchnic) and hepato-splanchnic blood flow changes were calculated. RESULTS: Vasopressin alone did not affect PVP, whereas HVP increased slightly. In combination with nitroglycerin, PVP decreased from 10.1 ± 1.6 to 8.9 ± 1.3 mmHg (P < 0.0001), and HVP decreased from 7.9 ± 1.9 to 6.2 ± 1.3 mmHg (P = 0.001). Vasopressin reduced portal blood flow by 47 ± 19% and hepatic venous flow by 11 ± 18%, respectively. Addition of nitroglycerin further reduced portal- and hepatic flow by 55 ± 13% and 30 ± 13%, respectively. Vasopressin alone had minor effects on central haemodynamics, whereas addition of nitroglycerin reduced cardiac index (3.2 ± 0.7 to 2.7 ± 0.5; P < 0.0001). The arterial-portal vein lactate gradient was unaffected. CONCLUSION: The combination of vasopressin and nitroglycerin decreases portal pressure and hepato-splanchnic blood flow, and could be a potential treatment to reduce bleeding in liver resection surgery.

Evaluation of a method for isocapnic hyperventilation: a clinical pilot trial.

BACKGROUND: Isocapnic hyperventilation (IHV) is a method that shortens time to extubation after inhalation anaesthesia using hyperventilation (HV) without lowering airway CO2 . In a clinical trial on patients undergoing long-duration sevoflurane anaesthesia for major ear-nose-throat (ENT) surgery, we evaluated the utility of a technique for CO2 delivery (DCO2 ) to the inspiratory limb of a closed breathing circuit, during HV, to achieve isocapnia. METHODS: Fifteen adult ASA 1-3 patients were included. After end of surgery, mechanical HV was started by doubling baseline minute ventilation. Simultaneously, CO2 was delivered and dosed using a nomogram developed in a previous experimental study. Time to extubation and eye opening was recorded. Inspired (FICO2 ) and expired (FETCO2 ) CO2 and arterial CO2 levels were monitored during IHV. Cognition was tested pre-operatively and at 20, 40 and 60 min after surgery. RESULTS: A DCO2 of 285 ± 45 ml/min provided stable isocapnia during HV (13.5 ± 4.1 l/min). The corresponding FICO2 level was 3.0 ± 0.3%. Time from turning off the vaporizer (1.3 ± 0.1 MACage) to extubation (0.2 ± 0.1 MACage) was 11.3 ± 1.8 min after 342 ± 131 min of anaesthesia. PaCO2 and FETCO2 remained at normal levels during and after IHV. In 85% of the patients, post-operative cognition returned to pre-operative values within 60 min. CONCLUSIONS: In this cohort of patients, a DCO2 nomogram for IHV was validated. The patients were safely extubated shortly after discontinuing long-term sevoflurane anaesthesia. Perioperatively, there were no adverse effects on arterial blood gases or post-operative cognition. This technique for IHV can potentially be used to decrease emergence time from inhalation anaesthesia.

Load-dependence of myocardial deformation variables - a clinical strain-echocardiographic study.

BACKGROUND: The effects of left ventricular (LV) loading on myocardial deformation variables are not well-studied in the clinical setting. In the present study, we evaluated the effects of isolated changes in preload, afterload and heart rate on LV longitudinal strain, systolic (SR-S) and early diastolic strain rate (SR-E) in post-cardiac surgery patients. METHODS: Twenty-one patients were studied early after cardiac surgery. Longitudinal myocardial strain and SR were analysed off-line using 2-D speckle echocardiography. The experimental protocol consisted of three consecutive interventions: (1) preload was increased by passive leg elevation, (2) afterload was increased by an infusion of phenylephrine to increase arterial blood pressure by 10-15% and (3) heart rate was increased 10% and 20% by atrial pacing. During both the preload and afterload challenges heart rate was kept constant by atrial pacing. Central venous pressure was kept constant during pacing by infusion of hetastarch/albumin. RESULTS: The increase in preload increased LV strain, SR-S and SR-E by 20%, 11% and 17%, respectively. The phenylephrine-induced increase in afterload, did not affect LV strain, SR-S or SR-E. LV strain was not affected while SR-S and SR-E increased by pacing-induced heart rate increase. CONCLUSION: After cardiac surgery, systolic and early diastolic strain rate are dependent on both preload and heart rate, while neither of these variables was afterload-dependent. LV strain was preload-dependent but not affected by atrial pacing. When evaluating the direct effects of various pharmacological or other interventions on myocardial contractility and relaxation, preload and heart rate must be controlled.

Takotsubo syndrome in hemodynamically unstable patients admitted to the intensive care unit - a retrospective study.

INTRODUCTION: Takotsubo syndrome (TS) is an acute cardiac condition that is often triggered by critical illness but that has rarely been studied in the intensive care unit (ICU) setting. The aim of this study was to (i) estimate the incidence of TS in a hemodynamically unstable ICU-population; (ii) identify predictors of TS in this population; (iii) study the impact of TS on prognosis and course of hospitalization. METHODS: Medical records from all patients admitted to our general ICU from 2012 to 2015 were analyzed. TS was defined as having transient regional wall motion abnormalities (RWMA) with a typical pattern not attributable to a history of coronary artery disease or acute coronary syndromes. RESULTS: Out of 6470 patients admitted to the ICU, echocardiography due to hemodynamic instability was performed in 1051 patients; 467 had LV dysfunction and 59 fulfilled TS criteria. Patients with TS had higher SAPS 3 scores on admission than patients with normal LV function. Septic shock, cardiac arrest, cerebral mass lesion, female sex and low pH were independently associated with TS on admission. Patients with TS needed more ICU resources measured by higher NEMS scores and longer ICU-stay. Crude mortality was higher in TS patients (32%) vs the ICU-population (20%, P = 0.020), but there were no differences in a SAPS 3 adjusted analysis. CONCLUSION: TS was not an uncommon cause of LV dysfunction in hemodynamically unstable ICU-patients. Furthermore, TS was associated with a more complex disease. TS is a complication to take in consideration in the critically ill.

Renal tubular injury during cardiopulmonary bypass as assessed by urinary release of N-acetyl-ß-D-glucosaminidase.

BACKGROUND: Acute kidney injury (AKI) is a common complication with a major impact on morbidity and mortality after cardiac surgery with cardiopulmonary bypass (CPB). The aim of the present study was to perform a detailed analysis on the release of the tubular injury biomarker N-acetyl-b-D-glucosaminidase (NAG) during and early after CPB and to describe independent predictors of maximal tubular injury. We hypothesized that renal tubular injury occurs early after the onset of CPB. METHODS: In this prospective observational study, we included 61 patients undergoing open cardiac surgery with an expected CPB duration exceeding 60 min. The urinary NAG levels were measured at 30 min intervals during CPB, as well as early (30 min) after CPB and post-operatively. Independent predictors of tubular injury were identified using an Interquantile multivariate regression model. RESULTS: Already 30 min after the onset of CPB, NAG excretion was significantly increased (P < 0.001), followed by a sixfold peak increase after discontinuation of CPB (P < 0.001). In the multivariable regression model, CPB duration (P < 0.05) and the degree of rewarming during CPB (P < 0.05), were independent predictors of peak NAG excretion. CONCLUSION: In cardiac surgery, a renal tubular cell injury is seen early after onset of CPB with a peak biomarker increase early after end of CPB. The magnitude of this tubular injury is independently related to CPB duration and the degree of rewarming. Efforts made to decrease the CPB duration and to avoid hypothermia and the need for rewarming may decrease the risk for tubular injury.

Early treatment with isoflurane attenuates left ventricular dysfunction and improves survival in experimental Takotsubo.

BACKGROUND: Takotsubo syndrome (TS) is an acute cardiac condition, often triggered by critical illness, for which no specific treatment exists. Previously, we showed that isoflurane can prevent experimental TS. The aim of this study was to evaluate the potential treatment effects of isoflurane. Our primary hypothesis was that early treatment with isoflurane attenuates left ventricular akinesia in experimental TS. METHOD: In propofol-sedated animals, TS was induced by an intraperitoneal bolus of isoprenaline (50 mg/kg). Animals were randomized to one of six groups (n = 15 in each group), and 1% isoflurane was administered for 90 min in all groups. Isoflurane treatment was started at 0, 10, 30 (early treatment) or 120 (late treatment) minutes after isoprenaline injection. One additional late treatment group received isoflurane 0.5% for 180 min. A control group did not receive isoflurane. Left ventricular (LV) echocardiographic examination was performed at 90 min and 48 h after isoprenaline. Mortality was assessed at 48 h. RESULTS: Median degree of LV akinesia at 90 min was 24% in the control group and 0% in the early treatment groups (P < 0.001). Stroke volume, cardiac output and LV ejection fraction were higher in the early treatment groups vs. controls (P < 0.01). Mortality was lower in the early treatment groups (24%) vs. controls (86%) (P < 0.001). Mortality did not differ between the late treatment groups and controls. CONCLUSION: Early treatment with isoflurane attenuates the LV akinesia and improves survival in experimental TS. Isoflurane sedation in patients at risk of developing Takotsubo syndrome could be a subject for future studies.

Anaesthetic-induced cardioprotection in an experimental model of the Takotsubo syndrome - isoflurane vs. propofol.

BACKGROUND: Takotsubo syndrome (TS) is an acute cardiac condition with a substantial mortality for which no specific treatment is available. We have previously shown that isoflurane attenuates the development of left ventricular (LV) dysfunction in an experimental TS-model. We compared the effects of equi-anaesthetic doses of isoflurane, propofol and ketamine+midazolam on haemodynamics, global and regional LV systolic function and the activation of intracellular metabolic pathways in experimental TS. We hypothesized that cardioprotection in experimental TS is specific for isoflurane. METHODS: Forty-five rats were randomized to isoflurane (0.6 MAC, n = 15), propofol (bolus 200 mg/kg+360 mg/kg/h, n = 15) or ketamine (100 mg/kg)+midazolam (10 mg/kg, n = 15) anaesthesia. Arterial pressure, heart rate and body temperature were continuously measured and arterial blood gas analysis was performed intermittently. TS was induced by intraperitoneal injection of isoprenaline, 50 mg/kg. LV echocardiography was performed 90 min after isoprenaline injection. Apical cardiac tissue was analysed by global discovery proteomics and pathway analysis. RESULTS: Isoprenaline-induced changes in arterial blood pressure, heart rate or body temperature did not differ between groups. LV ejection fraction was higher and extent of LV akinesia was lower with isoflurane, when compared with the propofol and the ketamine+midazolam groups. In this TS-model, the proteomic analysis revealed an up-regulation of pathways involved in inflammation, coagulation, endocytosis and lipid metabolism. This up-regulation was clearly attenuated with isoflurane compared to propofol. CONCLUSION: In an experimental model of TS, isoflurane, but not propofol, exerts a cardioprotective effect. The proteomic analysis suggests that inflammation might be involved in pathogenesis of TS.

Hyperbaric oxygen treatment reverses radiation induced pro-fibrotic and oxidative stress responses in a rat model.

PURPOSE: Radiotherapy is effective in the treatment of tumors in the pelvic area but is associated with side effects such as cystitis and proctitis. Hyperbaric Oxygen Therapy (HBOT) has emerged as a treatment modality for radiation-induced side effects. In a rat model for radiation cystitis, we studied the effects of HBOT on oxidative stress and pro-fibrotic factors. MATERIALS AND METHODS: Sedated Sprague-Dawley rats underwent bladder irradiation of 20Gy with and without 20 sessions of HBOT during a fortnight. Control animals were treated with and without HBOT. All four groups of animals were euthanized 28 days later. Histopathological examinations, immunohistochemistry and quantitative polymerase chain reaction (qPCR) were used to analyze changes in oxidative stress (8-OHdG), anti-oxidative responses (SOD-1, SOD2, HO-1 and NRFα) and a panel of Th1-type and Th2-type cytokines (IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-α, TGF-ß, IFN-γ) in the urinary bladder. RESULTS: Bladder irradiation increased the expression of 8-OHdG, SOD2, HO-1, NRFα, IL-10, TNF-α and tended to increase TGF-ß. These changes were completely reversed by HBOT while HBOT in control animals had no effects on the studied markers for oxidative stress, anti-oxidative responses and Th1-type and Th2-type cytokines. CONCLUSIONS: Radiation induced a significant elevation of oxidative stress, antioxidants and pro-fibrotic factors in our animal model for radiation cystitis that were completely reversed and normalized by HBOT. Our findings indicate that HBOT may prevent radiation-induced changes by affecting oxidative stress and inflammatory cascades induced by radiation. SUMMARY: Radiotherapy may cause the development of chronic inflammation and fibrosis, significantly impairing organ function. We hypothesized that bladder irradiation induces an oxidative stress reaction, thereby triggering the redox system and thus initiating an inflammatory and pro-fibrotic response. We aimed to assess whether these changes would be reversed by hyperbaric oxygen using an animal model for radiation cystitis. Our study show that hyperbaric oxygen therapy may reverse oxidative stress and pro-inflammatory factors induced by radiation.

Isocapnic hyperventilation shortens washout time for sevoflurane - an experimental in vivo study.

BACKGROUND: Isocapnic hyperventilation (IHV) is a method that fastens weaning from inhalation anaesthesia by increasing airway concentration of carbon dioxide (CO2 ) during hyperventilation (HV). In an animal model, we evaluated a technique of adding CO2 directly to the breathing circuit of a standard anaesthesia apparatus. METHODS: Eight anaesthetised pigs weighing 28 ± 2 kg were intubated and mechanically ventilated. From a baseline ventilation of 5 l/min, HV was achieved by doubling minute volume and fresh gas flow. Respiratory rate was increased from 15 to 22/min. The CO2 absorber was disconnected and CO2 was delivered (DCO2 ) to the inspiratory limb of a standard breathing circuit via a mixing box. Time required to decrease end-tidal sevoflurane concentration from 2.7% to 0.2% was defined as washout time. Respiration and haemodynamics were monitored by blood gas analysis, spirometry, electric impedance tomography and pulse contour analysis. RESULTS: A DCO2 of 261 ± 19 ml/min was necessary to achieve isocapnia during HV. The corresponding FICO2 -level remained stable at 3.1 ± 0.3%. During IHV, washout of sevoflurane was three times faster, 433 ± 135 s vs. 1387 ± 204 s (P < 0.001). Arterial CO2 tension and end-tidal CO2 , was 5.2 ± 0.4 kPa and 5.6 ± 0.4%, respectively, before IHV and 5.1 ± 0.3 kPa and 5.7 ± 0.3%, respectively, during IHV. CONCLUSIONS: In this experimental in vivo model of isocapnic hyperventilation, the washout time of sevoflurane anaesthesia was one-third compared to normal ventilation. The method for isocapnic hyperventilation described can potentially be transferred to a clinical setting with the intention to decrease emergence time from inhalation anaesthesia.

Vasopressin-induced changes in splanchnic blood flow and hepatic and portal venous pressures in liver resection.

BACKGROUND: To minimize blood loss during hepatic surgery, various methods are used to reduce pressure and flow within the hepato-splanchnic circulation. In this study, the effect of low- to moderate doses of vasopressin, a potent splanchnic vasoconstrictor, on changes in portal and hepatic venous pressures and splanchnic and hepato-splanchnic blood flows were assessed in elective liver resection surgery. METHODS: Twelve patients were studied. Cardiac output (CO), stroke volume (SV), mean arterial (MAP), central venous (CVP), portal venous (PVP) and hepatic venous pressures (HVP) were measured, intraoperatively, at baseline and during vasopressin infusion at two infusion rates (2.4 and 4.8 U/h). From arterial and venous blood gases, the portal (splanchnic) and hepato-splanchnic blood flow changes were calculated, using Fick's equation. RESULTS: CO, SV, MAP and CVP increased slightly, but significantly, while systemic vascular resistance and heart rate remained unchanged at the highest infusion rate of vasopressin. PVP was not affected by vasopressin, while HVP increased slightly. Vasopressin infusion at 2.4 and 4.8 U/h reduced portal blood flow (-26% and -37%, respectively) and to a lesser extent hepato-splanchnic blood flow (-9% and -14%, respectively). The arterial-portal vein lactate gradient was not significantly affected by vasopressin. Postoperative serum creatinine was not affected by vasopressin. CONCLUSION: Short-term low to moderate infusion rates of vasopressin induced a splanchnic vasoconstriction without metabolic signs of splanchnic hypoperfusion or subsequent renal impairment. Vasopressin caused a centralization of blood volume and increased cardiac output. Vasopressin does not lower portal or hepatic venous pressures in this clinical setting.

A simple method for isocapnic hyperventilation evaluated in a lung model.

BACKGROUND: Isocapnic hyperventilation (IHV) has the potential to increase the elimination rate of anaesthetic gases and has been shown to shorten time to wake-up and post-operative recovery time after inhalation anaesthesia. In this bench test, we describe a technique to achieve isocapnia during hyperventilation (HV) by adding carbon dioxide (CO2) directly to the breathing circuit of a standard anaesthesia apparatus with standard monitoring equipment. METHODS: Into a mechanical lung model, carbon dioxide was added to simulate a CO2 production (V(CO2)) of 175, 200 and 225 ml/min. Dead space (V(D)) volume could be set at 44, 92 and 134 ml. From baseline ventilation (BLV), HV was achieved by doubling the minute ventilation and fresh gas flow for each level of V(CO2), and dead space. During HV, CO2 was delivered (D(CO2)) by a precision flow meter via a mixing box to the inspiratory limb of the anaesthesia circuit to achieve isocapnia. RESULTS: During HV, the alveolar ventilation increased by 113 ± 6%. Tidal volume increased by 20 ± 0.1% during IHV irrespective of V(D) and V(CO2) level. D(CO2) varied between 147 ± 8 and 325 ± 13 ml/min. Low V(CO2) and large V(D) demanded a greater D(CO2) administration to achieve isocapnia. The FICO2 level during IHV varied between 2.3% and 3.3%. CONCLUSION: It is possible to maintain isocapnia during HV by delivering carbon dioxide through a standard anaesthesia circuit equipped with modern monitoring capacities. From alveolar ventilation, CO2 production and dead space, the amount of carbon dioxide that is needed to achieve IHV can be estimated.

Effects of acute plasma volume expansion on renal perfusion, filtration, and oxygenation after cardiac surgery: a randomized study on crystalloid vs colloid.

BACKGROUND: In the present randomized study, we evaluated the differential effects of a colloid and a crystalloid fluid on renal oxygen delivery (RD(O2)), glomerular filtration (GFR), renal oxygen consumption ((RV(O2))), and the renal oxygen supply-demand relationship (i.e., renal oxygenation) after cardiac surgery with cardiopulmonary bypass. METHODS: Thirty patients with normal preoperative renal function, undergoing uncomplicated cardiac surgery, were studied in the intensive care unit in the early postoperative period. Patients were randomized to receive a bolus dose of either a crystalloid (Ringers-acetate 20 ml kg(-1), n=15) or a colloid solution (Venofundin) 10 ml kg(-1), n=15). Systemic haemodynamics were measured via a pulmonary artery catheter. Renal blood flow and GFR were measured by the renal vein retrograde thermodilution technique and by renal extraction of 51Cr-EDTA (=filtration fraction). Arterial and renal vein blood samples were obtained for measurements of renal oxygen delivery (RD(O2)) and RV(O2). Renal oxygenation was estimated from the renal oxygen extraction. RESULTS: Despite an increase in cardiac index and renal blood flow with both fluids, neither of the fluids improved RD(O2), because they both induced haemodilution. The GFR increased in the crystalloid (28%) but not in the colloid group. The crystalloid increased the filtration fraction (24%) and renal oxygen extraction (23%), indicating that the increase in GFR, the major determinant of RV(O2), was not matched by a proportional increase in RD(O2). CONCLUSIONS: Neither the colloid nor the crystalloid improved RD(O2) when used for postoperative plasma volume expansion. The crystalloid-induced increase in GFR was associated with impaired renal oxygenation, which was not seen with the colloid. CLINICAL TRIAL REGISTRATION: NCT01729364.