Frank Grüne

Effects of a hemoglobin-based oxygen carrier (HBOC-201) on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery

We conducted a pilot study to evaluate the effects of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After induction of anesthesia and isovolemic hemodilution with 1 L of lactated Ringers solution, 13 patients were randomly assigned to receive, within 30 min, 3 mL/kg of either HBOC-201 or 6% hydroxyethyl starch (HES). Monitored variables included invasive arterial and pulmonary artery pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic and pulmonary vascular resistance indices, oxygen delivery index (DO (2) I), oxygen consumption index (VO2 I), and oxygen extraction ratio (O2 ER). Thirty minutes after HBOC-201 infusion, mean arterial pressure, systemic vascular resistance index, and CI were 149% (P = 0.028), 169% (P = 0.046), and 75% (P = 0.046) of the preinfusion values, respectively. No significant changes were noticed in heart rate and pulmonary vascular resistance index. DO2 I and VO2 I, 30 min after the infusion of HBOC-201, were 79% (P = 0.046) and 76% (P = 0.028) of the preinfusion values, respectively, whereas CaO2 and O2 ER remained unaffected. We conclude that HBOC-201, at a dose of 3 mL/kg, impairs oxygen delivery because of adverse effects on cardiac output. (Anesth Analg 1996;83:921-7)

The Effects of Increased Doses of Bovine Hemoglobin on Hemodynamics and Oxygen Transport in Patients Undergoing Preoperative Hemodilution for Elective Abdominal Aortic Surgery

In two consecutive studies (Study A and Study B), we evaluated the effects of increasing doses of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After the induction of anesthesia and the exchange of 1 L of blood for 1 L of lactated Ringers solution, 24 patients (12 in each study) were randomly assigned to receive, within 30 min, a predetermined volume of either HBOC-201 or 6% hydroxyethyl starch (Study A 6.9 mL/kg; Study B 9.2 mL/kg). Monitored variables included systemic and pulmonary arterial pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic (SVRI) and pulmonary (PVRI) vascular resistance indices, oxygen delivery index (Do2 I), oxygen consumption index (Vo2 I), and oxygen extraction ratio (O2 ER). In both studies, the infusion of HBOC-201 was associated with increases in SVRI (Study A 121%; Study B 71%) and PVRI (Study A 70%; Study B 53%) and with a decrease in CI (29% both studies). Hemodilution with HBOC-201 maintained the arterial oxygen content at levels higher than hemodilution with hydroxyethyl starch, but the advantage of a greater oxygen-carrying capacity was offset by the increase in SVRI, with a resulting net decrease in both CI and Do2 I (Study A 30%; Study B 28%); Vo2 I was maintained by increased O2 ER. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch. Implications: Bovine hemoglobin in doses ranging between 55 and 97 g of hemoglobin increased vascular resistance and decreased cardiac output in anesthetized surgical patients. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch. (Anesth Analg 1998;87:284-91)

Flow velocity measurements as an index of cerebral blood flow. Validity of transcranial Doppler sonographic monitoring during cardiac surgery.

Background:Transcranial Doppler sonography is increasingly used to monitor changes in cerebral perfusion intraoperatively. However, little information is available about the validity of velocity measurements as an index of cerebral blood flow (CBF). The purpose of this study was to compare invasive and Doppler-derived measurements of cerebral hemodynamic variables during coronary artery bypass graft surgery. Methods:In 15 male patients, measurements of CBF and middle cerebral artery flow velocity (VMCA) were performed before and after induction of fentanyl-midazolam anesthesia, during hypothermic cardiopulmonary bypass (CPB), and at the end of the surgical procedure. Transcranial Doppler sonography recordings of systolic, diastolic, and mean VMCA, and derived parameters such as pulsatility (PI) and resistance (RI) indexes were recorded from the proximal segment of the right middle cerebral artery. CBF was measured by the Kety-Schmidt inert gas saturation method with argon as a tracer. To facilitate comparisons of CBF and VMCA measurements, changes between consecutive measurements were expressed as percentage values. Calculations of cerebral perfusion pressure and cerebral vascular resistance (CVR) were based on jugular bulb pressure. The cerebral metabolic rate for oxygen was calculated from CBF and the arterial — cerebral venous oxygen content difference. Results:Changes In mean VMCA paralleled changes in mean CBF except for hemodynamic changes associated with hypothermic CPB. At this stage of surgery, mean VMCA increased while actual CBF decreased. Separate analysis of the periods before and after CPB revealed a poor association between percentage changes In CBF and VMCA (r=0.26, P=0.36; r=0.51, P=0.06, respectively). Mean values of CVR, PI, and RI showed consistent changes after induction of anesthesia. After termination of CPB, mean CVR significantly decreased, whereas mean PI and RI remained virtually unchanged. Neither before nor after CPB was a clinically useful correlation found between percentage changes in PI, RI, and CVR (PI r=0.28, P=0.34; r=-0.47, P=0.09, respectively; RI r=0.16, P=0.59; r=-0.53, P=0.06, respectively). Conclusions:Hypothermic CPB seems to alter the relation between global CBF and flow velocity in basal cerebral arteries. Inconsistency in directional changes in CBF and VMCA at this stage of surgery might be attributable to changes in middle cerebral artery diameter, red blood cell velocity spectra, and regional flow distribution. Although changes in mean VMCA before and after CPB appear to parallel changes In mean CBF, individual responses of VMCA cannot reliably predict percentage changes in CBF. Furthermore, Doppler sonographic PI and RI cannot provide an approximation of changes in CVR during cardiac surgery.

Preoperative risk assessment and prevention of complications in patients with esophageal cancer

In this review the preoperative risk assessment and prevention of complications in patients undergoing esophagectomy for cancer is discussed. Age, pulmonary and cardiovascular condition, nutritional status, and neoadjuvant chemo(radio)therapy are known predictive factors. None of these factors is a valid exclusion criterion for esophagectomy, but may help in careful patient selection. Both anesthetists and surgeons play an important role in intraoperative risk reduction by means of appropriate fluid management and application of optimal surgical techniques. J. Surg. Oncol. 2010; 101:270–278.

Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial

BackgroundIn patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during orthotopic liver transplantation is currently managed by transfusion of red blood cell concentrates, platelet concentrates, fresh frozen plasma, and fibrinogen concentrate. Transfusion of these products may paradoxically result in an increased bleeding tendency due to aggravated portal hypertension. The hemostatic effect of these products may therefore be overshadowed by bleeding complications due to volume overload.In contrast to these transfusion products, prothrombin complex concentrate is a low-volume highly purified concentrate, containing the four vitamin K dependent coagulation factors. Previous studies have suggested that administration of prothrombin complex concentrate is an effective method to normalize a prolonged prothrombin time in patients with liver cirrhosis. We aim to investigate whether the pre-operative administration of prothrombin complex concentrate in patients undergoing liver transplantation for end-stage liver cirrhosis, is a safe and effective method to reduce perioperative blood loss and transfusion requirements.Methods/DesignThis is a double blind, multicenter, placebo-controlled randomized trial.Cirrhotic patients with a prolonged INR (≥1.5) undergoing liver transplantation will be randomized between placebo or prothrombin complex concentrate administration prior to surgery. Demographic, surgical and transfusion data will be recorded. The primary outcome of this study is RBC transfusion requirements.DiscussionPatients with advanced cirrhosis have reduced plasma levels of both pro- and anticoagulant coagulation proteins. Prothrombin complex concentrate is a low-volume plasma product that contains both procoagulant and anticoagulant proteins and transfusion will not affect the volume status prior to the surgical procedure. We hypothesize that administration of prothrombin complex concentrate will result in a reduction of perioperative blood loss and transfusion requirements. Theoretically, the administration of prothrombin complex concentrate may be associated with a higher risk of thromboembolic complications. Therefore, thromboembolic complications are an important secondary endpoint and the occurrence of this type of complication will be closely monitored during the study.Trial registrationThe trial is registered at http://www.trialregister.nl with number NTR3174. This registry is accepted by the ICMJE.

Lorazepam does not improve the quality of recovery in day-case surgery patients: a randomised placebo-controlled clinical trial.

BACKGROUND In day-case surgery, the effects of the anxiolytic lorazepam as premedication on the quality of postoperative recovery are unknown. OBJECTIVE To evaluate whether lorazepam as a premedication beneficially affects quality of recovery (primary outcome) and psychological manifestations (secondary outcome) after day-case surgery. DESIGN A randomised, double-blind, placebo-controlled clinical trial. SETTING Single tertiary centre. PATIENTS Inclusion criteria: day-case surgery; age at least 18 years. Exclusion criteria: insufficient knowledge of the Dutch language; intellectual disability; ophthalmology surgery; extracorporeal shock wave lithotripsy; endoscopy; botulinum toxin A treatment; abortion; chronic pain treatment; preceding use of psychopharmaceuticals; contraindication to lorazepam. INTERVENTION Lorazepam (1 to 1.5 mg) intravenously vs. NaCl 0.9% as a premedication prior to surgery. MAIN OUTCOME MEASURE Quality of Recovery-40 (QoR-40) score. Secondary outcomes: State-Trait Anxiety Inventory (STAI-State/Trait); State-Trait Anger Scale (STAS-State/Trait); Multidimensional Fatigue Inventory (MFI); Hospital Anxiety and Depression Scale (HADS). Timing of evaluation: T0: preoperatively (all scales); T1: before discharge (STAI-State/Trait); T2: first postoperative working day (QoR-40); T3: 7th day after surgery (all scales). Robust regression analysis was applied. Statistical analyses were adjusted for the corresponding baseline value and sex. RESULTS Four hundred patients were randomised; 398 patients were analysed. Postoperative mean QoR-40 scores were similar in both groups at T2 (174.5 vs. 176.4, P = 0.34) and T3 (172.8 vs.176.3, P = 0.38). Postoperative mean STAI-State/Trait scores decreased less in the group with lorazepam at T1 (32.3 vs. 29.3, P < 0.0001; 32.7 vs. 30.8, P = 0.0002). STAI-Trait and HADS-Anxiety decreased less in the group with lorazepam at T3 (31.1 vs. 30.0; P = 0.03, 3.3 vs. 2.5, P = 0.003). STAS-State increased in the group with lorazepam at T3 (10.8 vs. 10.3, P = 0.04). CONCLUSION In day-case surgery, lorazepam as a premedication did not improve quality of recovery. Furthermore, this premedication may delay the decrease in postoperative anxiety and aggression. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01441843.

Effect of ketanserin on global cerebral blood flow and middle cerebral artery flow velocity

The aim of this study was to examine the influence of ketanserin, a 5-hydroxytryptamine antagonist antihypertensive agent, on the relationship between cerebral blood flow (CBF) and middle cerebral artery flow velocity (Vmean MCA) and to compare Doppler-sonographic indices of downstream resistance (pulsatility index, PI; resistance index, RI) with calculations of cerebrovascular resistance (CVR) in 17 male patients under fentanyl/midazolam anesthesia. CBF was measured with the Kety-Schmidt technique using argon as a tracer. Cerebral perfusion pressure (CPP) was calculated as the difference between mean arterial pressure (MAP) and jugular bulb pressure. Measurements of Vmean MCA and determinations of PI and RI were performed by use of a 2-MHz transcranial Doppler ultrasound device. All variables were measured at normo- and moderate hypocapnia before and after intravenous (IV) bolus administration of 0.3 mg/kg ketanserin followed by an infusion of 0.06 mg centered dot kg-1 centered dot h-1. Ketanserin changed neither average CBF nor Vmean MCA. The CO2 reactivity of Vmean MCA was significantly lower than the CO2 reactivity of CBF (P < 0.01); however, ketanserin did not change the relationship between CBF and Vmean MCA. During hypocapnia, CVR as well as PI and RI significantly increased (P <or=to 0.01), indicating consistent directional changes in arteriolar resistance and flow velocity pulsatility. In contrast, after IV administration of ketanserin, CVR decreased (P < 0.05), whereas both Doppler-derived indices increased (P < 0.01). These results suggest that ketanserin in a clinically relevant dose does not alter the validity of serial Vmean MCA measurements as an index of global CBF and that ketanserin does not change the diameter of middle cerebral arteries (MCAs). Doppler-derived indices of pulsatility and resistance, which are supposed to estimate changes in downstream resistance, reflect changes, after administration of ketanserin, in systemic hemodynamics rather than changes in CVR. (Anesth Analg 1995;80:64-70)

Moderate hyperventilation during intravenous anesthesia increases net cerebral lactate efflux

Background:Hyperventilation is known to decrease cerebral blood flow (CBF) and to impair cerebral metabolism, but the threshold in patients undergoing intravenous anesthesia is unknown. The authors hypothesized that reduced CBF associated with moderate hyperventilation might impair cerebral aerobic metabolism in patients undergoing intravenous anesthesia. Methods:Thirty male patients scheduled for coronary surgery were included in a prospective, controlled crossover trial. Measurements were performed under fentanyl-midazolam anesthesia in a randomized sequence aiming at partial pressures of carbon dioxide of 30 and 50 mmHg. Endpoints were CBF, blood flow velocity in the middle cerebral artery, and cerebral metabolic rates for oxygen, glucose, and lactate. Global CBF was measured using a modified Kety–Schmidt technique with argon as inert gas tracer. CBF velocity of the middle cerebral artery was recorded by transcranial Doppler sonography. Data were presented as mean (SD). Two-sided paired t tests and one-way ANOVA for repeated measures were used for statistical analysis. Results:Moderate hyperventilation significantly decreased CBF by 60%, blood flow velocity by 41%, cerebral oxygen delivery by 58%, and partial pressure of oxygen of the jugular venous bulb by 45%. Cerebral metabolic rates for oxygen and glucose remained unchanged; however, net cerebral lactate efflux significantly increased from −0.38 (2.18) to −2.41(2.43) µmol min−1 100 g−1. Conclusions:Moderate hyperventilation, when compared with moderate hypoventilation, in patients with cardiovascular disease undergoing intravenous anesthesia increased net cerebral lactate efflux and markedly reduced CBF and partial pressure of oxygen of the jugular venous bulb, suggesting partial impairment of cerebral aerobic metabolism at clinically relevant levels of hypocapnia.

Cerebral perfusion pressure in women with preeclampsia is elevated even after treatment of elevated blood pressure

Cerebral perfusion pressure (CPP) is elevated in preeclampsia, and may predispose to cerebrovascular complications and progression to eclampsia. We estimated zero flow pressure (ZFP) and CPP using simultaneously obtained arterial blood pressure and middle cerebral artery blood flow velocity in 10 women with preeclampsia, all treated with methyldopa with or without nifedipine, and 18 healthy pregnant controls. Mean ± SD ZFP was lower in women with preeclampsia than in controls (16.8 ± 10.9 vs. 31.7 ± 15.0 mmHg, p = 0.01) whereas CPP was considerably higher (82.3 ± 17.7 vs. 55.0 ± 11.7 mmHg, p < 0.001), as was the cerebral flow index (41.9 ± 18.0 vs. 25.6 ± 11.2, p = 0.02). There was a significant correlation between blood pressure and CPP in women with preeclampsia, but not in controls. Women with preeclampsia may have an increased cerebral perfusion due to a reduced ZFP and increased CPP despite treatment with antihypertensive medication. More rigorous antihypertensive therapy, aimed at reducing CPP, could result in a decrease in cerebral complications in women with preeclampsia.

Kardiale Vorlast und zentraler Venendruck

The force of cardiac contraction is strongly influenced by myocardial fibre length at the beginning of systole. Because the length of cardiac sarcomers and muscle fibres primarily depends on the end-diastolic ventricular volume, filling pressures a priori can only act as indirect parameters of cardiac preload. Central venous pressure (CVP) gives information on right ventricular end-diastolic pressure, which parallels changes in left ventricular end-diastolic pressure as long as ventricular function is not impaired. Since the pressure-volume relationship of cardiac ventricles is not linear and shows great variability, filling of the ventricles cannot be directly derived from end-diastolic pressure. Further limitations of CVP as a surrogate variable of preload are caused by the influence of intrathoracic and intra-abdominal pressures. A valid parameter of preload should describe the relationship between preload and stroke volume as given by the Frank-Starling law. Furthermore, estimates of cardiac preload should enable prediction of fluid responsiveness. Many studies have demonstrated that under clinical conditions CVP cannot meet these demands and thus does not appear to be a useful predictor of cardiac preload. Variables which more directly represent end-diastolic ventricular volume (e.g. intrathoracic blood volume or end-diastolic ventricular area) offer a higher validity as estimates of cardiac preload. Furthermore, dynamic parameters of ventricular preload, such as pulse pressure variation or stroke volume variation, seem to be more predictive of volume responsiveness in ventilated patients than CVP. These limitations, however, do not impair the importance of CVP as the downstream pressure of the systemic venous system.ZusammenfassungDa die Kontraktionskraft des Herzmuskels von der Vordehnung der myokardialen Sarkomere abhängt und deren Länge am intakten Herzen primär vom ventrikulären enddiastolischen Volumen bestimmt wird, können Füllungsdrücke a priori nur indirekte Parameter der Vorlast darstellen. Der zentrale Venendruck („central venous pressure“, CVP) liefert Informationen über den rechtsventrikulären enddiastolischen Druck, dessen Änderungen nur bei weitgehend ungestörter Ventrikelfunktion direkt Änderungen des linksventrikulären enddiastolischen Drucks widerspiegeln. Da die Druck-Volumen-Beziehung der Ventrikel nicht linear ist und darüber hinaus inter- sowie auch intraindividuell einer hohen Variabilität unterworfen ist, ist ein direkter Rückschluss von den enddiastolischen Drücken auf die Füllung der Ventrikel kaum möglich. Weitere Limitationen des CVP als Surrogatvariable der kardialen Vorlast sind insbesondere bei kritisch kranken Patienten durch den Einfluss des intrathorakalen und des intraabdominellen Drucks gegeben. Ein valider Vorlastparameter sollte den durch den Frank-Starling-Mechanismus gegebenen Zusammenhang zum Schlagvolumen (SV) bzw. zum Herzzeitvolumen (HZV) abbilden und darüber hinaus eine Vorhersage ermöglichen, inwieweit eine Volumengabe zu einer Erhöhung des HZV führt. Zahlreiche Untersuchungen zeigen, dass der CVP unter klinischen Bedingungen diese Anforderungen nicht erfüllt und zur Abschätzung der ventrikulären Vorlast somit kaum geeignet ist. Messgrößen, die auf direktere Weise das links- und rechtsventrikuläre enddiastolische Volumen abbilden, weisen eine höhere Aussagekraft hinsichtlich der kardialen Vorlast auf. Für die Abschätzung der Volumenreagibilität des beatmeten Patienten sind ferner dynamische Vorlastparameter wie die Pulsdruckvariation und die SV-Variation dem CVP überlegen. Die gravierenden Einschränkungen bei der Interpretation als Vorlastparameter beeinträchtigen jedoch nicht die Bedeutung des CVP als Abflussdruck für das venöse System der systemischen Zirkulation.AbstractThe force of cardiac contraction is strongly influenced by myocardial fibre length at the beginning of systole. Because the length of cardiac sarcomers and muscle fibres primarily depends on the end-diastolic ventricular volume, filling pressures a priori can only act as indirect parameters of cardiac preload. Central venous pressure (CVP) gives information on right ventricular end-diastolic pressure, which parallels changes in left ventricular end-diastolic pressure as long as ventricular function is not impaired. Since the pressure-volume relationship of cardiac ventricles is not linear and shows great variability, filling of the ventricles cannot be directly derived from end-diastolic pressure. Further limitations of CVP as a surrogate variable of preload are caused by the influence of intrathoracic and intra-abdominal pressures. A valid parameter of preload should describe the relationship between preload and stroke volume as given by the Frank-Starling law. Furthermore, estimates of cardiac preload should enable prediction of fluid responsiveness. Many studies have demonstrated that under clinical conditions CVP cannot meet these demands and thus does not appear to be a useful predictor of cardiac preload. Variables which more directly represent end-diastolic ventricular volume (e.g. intrathoracic blood volume or end-diastolic ventricular area) offer a higher validity as estimates of cardiac preload. Furthermore, dynamic parameters of ventricular preload, such as pulse pressure variation or stroke volume variation, seem to be more predictive of volume responsiveness in ventilated patients than CVP. These limitations, however, do not impair the importance of CVP as the downstream pressure of the systemic venous system.