This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review of research conducted by Joachim Boldt at the University. This is further described in 'Further Retractions of Articles by Joachim Boldt', https://doi.org/10.1016/j.bja.2020.02.024.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review of research conducted by Joachim Boldt at the University. This is further described in 'Further Retractions of Articles by Joachim Boldt', https://doi.org/10.1016/j.bja.2020.02.024.

The above article, published online on 30 December 2008 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Prof. Lars S. Rasmussen, and John Wiley & Sons Ltd. The retraction has been agreed following an investigation carried out by the Justus Liebig University, which has concluded that there is evidence that the original research data on which the article builds has been manipulated. Reference Boldt J, Zickmann B, Rapin J, Hammermann H, Dapper F, Hempelmann G. Influence of volume replacement with different HES-solutions on microcirculatory blood flow in cardiac surgery. Acta Anaesthesiol Scand 1994; 38: 432-438. doi:.

In a randomized study of 30 patients undergoing elective aortocoronary bypass grafting, either cold start of cardiopulmonary bypass (CPB) (prime: room temperature [approximately 20°C], n = 15) or normothermic start of CPB (prime: warmed up to the patients' blood temperature, n = 15) were performed. After warm start, CPB was continued using almost normothermia (lowest nasopharyngeal temperature: 35.8 ± 0.4°C), after cold start hypothermia was used (lowest nasopharyngeal temperature: 28.8 ± 0.2°C). Changes in microcirculatory perfusion were assessed by measuring skin capillary blood flow at the patient's forearm and forehead using laser Doppler technique. Laser Doppler flow (LDF) was continuously monitored before onset of CPB (=baseline values), 30 seconds, one, five, 10, 15 and 20 minutes after start of CPB. Mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) were reduced by CPB in both groups, with the more pronounced reduction in the normothermic patients. Haemoglobin and plasma viscosity were without differences between the groups. The lowest blood temperature in the hypothermic patients was 21.0 ± 0.3°C, and the lowest rectal temperature in these patients was 29.0 ± 0.3°C (20 minutes after start of CPB). Forehead- and forearm-LDF increased significantly in both groups by start of CPB. In the hypothermic patients, this increase was significantly lower, and LDFs were already reduced below baseline values five to 10 minutes after onset of CPB (LDF-forehead -18%, LDF-forearm -72%). In the normothermic patients, LDFs remained elevated during the first 20 minutes after the beginning of bypass (LDF- forehead +38%; LDF-forearm +35%) and were significantly higher than baseline ' even after CPB (hypothermia: LDF-forehead -34%; LDF-forearm -31%). Except for the blood temperature, none of the measured haemodynamic and laboratory values could be related significantly to changes of LDFs (analyses of covariance). It is concluded that skin microcirculatory perfusion as assessed by laser Doppler flowmetry was less altered when using warm start and maintenance of perfusion than after cold start and hypothermic CPB. Whether this improvement in microperfusion after warm start of CPB takes place also in other (more vital) organs has to be elucidated in further studies.

During anesthesia and in intensive care, pharmacological support is often required in patients with preexisting myocardial dysfunction as well as in patients with normal preoperative ventricular function. Abnormalities in both systolic and diastolic function may occur in this situation. Standard therapy used in this situation act on alpha-, beta- or dopaminergic-receptors. However, the observation of beta-receptor down-regulation phenomenon has led to the development of substances which act independently of the beta-receptor. The imidazole derivative enoximone belongs to a new class of non-catecholaminergic positive inotropics, which acts by selectively inhibiting phosphodiesterase type-III thus using a mechanism distal of the beta-receptor. Enoximone has been proven to successfully improve hemodynamics by either its positive inotropic and lusitropic or its vasodilating properties. The expected increase in MVO2 secondary to the increase in myocardial contractility appears to be compensated by the decrease in ventricular pre- and afterload. The most obvious positive hemodynamic effects are reported for patients undergoing cardiac surgery. In both adults and pediatric patients hemodynamics were improved significantly in this situation. There is a particular indication for enoximone for patients with severely impaired hemodynamics awaiting heart transplantation ("pharmacological" bridging). The first promising results were documented when PDE-III-inhibitors were given in myocardial infarction and septic shock patients. The most important risk associated with the use of enoximone is the reduction in blood pressure due to its arterial and venous vasodilatory effects. Limitation to a bolus of 0.5 mg/kg or a perfusor controlled therapy help to avoid critical decrease in perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin has been reported to reduce bleeding in cardiac surgery patients. Its mechanisms of action on coagulation have not been fully elucidated. In a prospectively randomized study of 40 patients undergoing elective aortocoronary bypass grafting, the influence of high-dose aprotinin (2 million IU of aprotinin before CPB, 500,000 IU/h until the end of operation, 2 million IU added to the prime) (N = 20) on endothelial-related coagulation was compared to a non-treated control group (N = 20). Thrombomodulin (TM), protein C and (free) protein S as well as thrombin/antithrombin-III (TAT) plasma concentrations were measured by enzyme-linked immunosorbent assays (ELISA) before the aprotinin infusion, before cardiopulmonary bypass (CPB), during CPB and after CPB, at the end of surgery, 5 hours after CPB, and on the first postoperative day. All standard coagulation parameters (AT-111 and fibrinogen plasma levels, platelet count, partial thromboplastin time) did not differ between the two groups. At baseline, TM plasma levels were within the normal range (<40 ng/mL) and similar in both groups. During CPB, TM plasma concentrations decreased similarly in both groups (aprotinin: 18 ± 6 ng/mL, control: 17 ± 7 ng/ mL) followed by a comparable increase in the postbypass period until the first postoperative day (aprotinin: 60 ± 10 ng/mL, control: 53 + 11 ng/mL). Protein C and (free) protein S plasma levels also showed no differences between the two groups. On the first postoperative day, baseline values for protein C and protein S had not yet been reached. At the end of surgery, TAT had increased more in the nontreated control (from 8 ± 3 μg/L to 90 ± 12 μg/L) than in the aprotinin-treated patients (from 10 ± 4 ng/L to 68 ± 13 μg/L) (P < 0.05). Postoperative blood loss and use of homologous blood were not different in either group. It is concluded that aprotinin did not influence endothelial-related coagulation. Neither TM nor protein C or (free) protein S plasma levels were significantly different from a nontreated control group.

During anesthesia and in intensive care, pharmacological support is often required in patients with preexisting myocardial dysfunction as well as in patients with normal preoperative ventricular function. Abnormalities in both systolic and diastolic function may occur in this situation. Standard therapy used in this situation act on alpha-, beta- or dopaminergic-receptors. However, the observation of beta-receptor down-regulation phenomenon has led to the development of substances which act independently of the beta-receptor. The imidazole derivative enoximone belongs to a new class of non-catecholaminergic positive inotropics, which acts by selectively inhibiting phosphodiesterase type-III thus using a mechanism distal of the beta-receptor. Enoximone has been proven to successfully improve hemodynamics by either its positive inotropic and lusitropic or its vasodilating properties. The expected increase in MVOP secondary to the increase in myocardial contractility appears to be compensated by the decrease in ventricular pre- and afterload. The most obvious positive hemodynamic effects are reported for patients undergoing cardiac surgery. In both adults and pediatric patients hemodynamics were improved significantly in this situation. There is a particular indication for enoximone for patients with severely impaired hemodynamics awaiting heart transplantation (''pharmacological'' bridging). The first promising results were documented when PDE-III-inhibitors were given in myocardial infarction and septic shock patients. The most important risk associated with the use of enoximone is the reduction in blood pressure due to its arterial and venous vasodilatory effects. Limitation to a bolus of 0.5 mg/kg or a perfusor controlled therapy help to avoid critical decrease in perfusion pressure. It seems to be senseless to use enoximone as a ''last-minute-drug'' in patients suffering from hemodynamic shock, which has proved refractory to catecholamines. Thus, it is recommended to use it as a first-line drug in patients with ''low output'' syndrome. The combination of adrenergic substances to increase the production of cyclic adenosine monophosphate with the PDE-III-inhibitor enoximone to inhibit its degradation seems to be an attractive concept for treating patients with impaired myocardial function.

Objective: Evaluation of continuous cardiac output monitoring based on the thermodilution technique in the critically ill. Design: Prospective clinical investigation. Setting: A surgical intensive care unit of a university hospital. Patients: Thirty-five critically ill patients (trauma and/or sepsis patients), who needed pulmonary artery catheterization. The patients were prospectively studied according to the following groups: a) patients with a heart rate of >120 beats/min; b) those patients with a cardiac output of >10 L/min; c) patients with a cardiac output of <4.5 L/min; d) patients with a rectal temperature of >39.0°C; and e) patients with a pulmonary artery catheter inserted for >4 days. Interventions: Therapies were carried out according to modern intensive care medicine protocols by physicians who were not involved in the study. Measurements: Cardiac output was monitored continuously using a new, modified pulmonary artery catheter. This catheter has a heating filament by which energy is transmitted to the circulating blood (modified thermodilution technique). A bedside microprocessor calculated cardiac output using a new algorithm. Standard bolus thermodilution technique (10 mL of ice-cold saline solution) was used to compare the continuous cardiac output measurement with the intermittent bolus cardiac output measurement. Main Results: A total of 404 pairs of intermittent (bolus) cardiac output and continuous cardiac output measurements were obtained from the 35 patients. The bias (mean difference between bolus cardiac output measurement and continuous cardiac output measurement) of all measurements was 0.03 ± 0.52 L/min and the 95% confidence limit (mean difference ± 2 sd) was -1.01/1.06 L/min. Also, continuous cardiac output measurement agreed closely with bolus cardiac output measurement (bias was 0.16 ± 0.57 L/min in the cardiac output of >10 L/min group; bias was -0.17 ± 0.50 L/min for the cardiac output of <4.5 L/min group). Increased temperature and prolonged length of stay did not influence the agreement of continuous cardiac output measurement with bolus cardiac output measurement (bias was 0.09 ± 0.51 L/min in the >39°C rectal temperature group). Conclusions: Continuous monitoring of cardiac output using a modified pulmonary artery catheter with a heated filament has proven to be accurate and precise in the critically ill patient when compared with the “standard” intermittent bolus thermodilution technique. The continuous monitoring technique enhances our armamentarium for more intensive monitoring of these patients under a variety of circumstances. (Crit Care Med 1994; 22:1913–1918)

A variety of hydroxyethyl starch (HES) preparations with different molecular weight average (Mw) and molar substitution (MS) is available for volume replacement during acute normovolemic haemodilution (ANH). Particularly with regard to microcirculation, the ideal solution for volume therapy has not been found. A 5th group without ANH served as a control (10 patients in each group). In addition to systemic haemodynamics and various laboratory parameters, skin capillary blood flow was measured by laser Doppler flowmetry. Laser Doppler flow (LDF) was monitored simultaneously at the patient's forehead and forearm. Changes in systemic haemodynamics were similar in all ANH–patients. Systemic vascular resistance (SVR) was lowest after infusion of HES 200/0.5. The most pronounced increase in plasma viscosity was in patients of group 1 (450/0.7) ( P <0.05) and plasma viscosity remained highest during the entire investigation period in these patients. After ANH, skin capillary blood flow measured at the forehead decreased in all patients except in patients of group 2 (200/0.5: max. + 18%). Group 3 (200/0.62) showed the highest decrease in forehead–LDF. During CPB, forehead–LDF decreased significantly in groups 3 (200/0.62) and 4 (40/0.5). At the end of the operation, LDF was most reduced in groups 1 (– 32%) and 3 (– 33%). Forearm–LDF increased in all ANH–patients. Immediately after ANH this increase was lowest in group 3 (200/0.62). In the further course of the investigation, no more differences were seen in any HES patients. The different HES preparations showed a different microcirculatory response. 6% HES 200/0.5 seems to be overall most suitable for volume replacement in cardiac surgery patients undergoing acute normovolemic haemodilution (ANH) due to the best effects on microcirculatory skin perfusion assessed by laser Doppler flow. HES 6% 200/0.62 showed the overall least positive effects with regard to skin capillary blood flow in this situation.

OBJECTIVE:To determine the cardiopulmonary actions of the intravenous administration of the angiotensin-converting enzyme inhibitor enalaprilat in hypertensive trauma patients. DESIGN:Prospective, before/after trial. SETTING:Intensive care unit (ICU) of a university hospital. PATIENTS:Twenty critically injured and hypertensive ICU patients. All patients were receiving continuous sedation (fentanyl and midazolam) for at least 2 days before the injection of enalaprilat and had a mean arterial pressure (MAP) of > 95 mm Hg. "Responders" were defined as having a decrease in MAP of > 15% within 30 mins after enalaprilat injection. INTERVENTIONS:Intravenous administration of 0.06 mg/kg of the angiotensin-converting enzyme inhibitor enalaprilat. Repeated doses were given when no sufficient response (decrease of MAP of > 15% within 30 mins after injection) was seen ("nonresponders"). MEASUREMENTS:In addition to standard hemodynamic monitoring, right ventricular hemodynamics and oximetric variables were also documented. Measurements were carried out before enalaprilat injection (during hemodynamic steady state [baseline values]) and at 1, 5, 10, 20, 30, 60, and 120 mins after enalaprilat administration. MAIN RESULTS:MAP was successfully controlled in 17 of 20 patients (maximum decrease -27 mm Hg [-26%]). In the three other patients, even reinjection of enalaprilat (0.06 mg/kg) did not sufficiently reduce MAP. In the 17 responders, heart rate did not increase, whereas central venous pressure, pulmonary arterial pressure, and pulmonary artery occlusion pressure decreased significantly after intravenous administration of enalaprilat. Cardiac index changed only slightly (mean maximum +0.70 L/min/m2 [+18%]). Right ventricular ejection fraction increased from 36% to 45% (p < .05); right ventricular end-diastolic and end-systolic volume index decreased significantly. Both systemic and pulmonary vascular resistance indices decreased within the investigation period (-31% and -16%, respectively). Pao2/FIO2, intrapulmonary right-to-left shunting, and oxygen extraction ratio were not altered. Oxygen delivery index (+17%) and oxygen consumption index (+20%) increased during the investigation period (p < .04). CONCLUSIONS:The intravenous administration of enalaprilat successfully decreased blood pressure in most of our patients. Mechanisms other than the renin-angiotensin system also appear to be involved in hypertensive, critically ill patients. Pulmonary function was not altered; right ventricular function, and both oxygen consumption and oxygen delivery improved in the enalaprilat responder group. Thus, the availability of intravenous enalaprilat seems to enlarge our armamentarium for treating hypertension in the critically ill patient.

Hypertonic saline solution appears to be an attractive method of volume expansion. In 45 patients undergoing elective aorto-coronary bypass grafting, endocrinologic and circulatory responses to volume loading with hypertonic saline solution prepared in low molecular weight (MW) hydroxyethyl starch (HES) solution (72 g/L NaCl, HES concentration: 6%; MW: 200,000 D; degree of substitution [DS]: 0.5) (HS-HES) was compared randomly to patients who had received low molecular weight HES solution (LMW-HES). A group of patients without volume loading served as a control. Volume was infused to double the low pulmonary capillary wedge pressure (PCWP < 5 mmHg) after induction of anesthesia. Plasma levels of atrial natriuretic peptide (ANP), endothelin, vasopressin, and catecholamines were measured before, during, and after cardiopulmonary bypass (CPS) until the first postoperative day. In addition to systemic circulatory changes, capillary skin blood flow was measured by laser Doppler flowmetry. ANP plasma concentration increased in both volume groups (HS-HES: +79%; HES: +32%), whereas it decreased in the control (−20%). Infusion of HS-HES resulted in an increase in plasma endothelin concentration before and after CPS (from 3 to 6 pg/mL). Five hours after CPB, both treatment groups had higher endothelin plasma concentrations than the control patients (P < 0.05). Epinephrine and norepinephrins plasma levels increased most markedly in the control patients and were highest in the postbypass period in these patients. Cl increased most after infusion of HS-HES (+65%) (P < 0.05). In the postbypass period, Cl remained significantly higher in both volume groups than in the controls. SVR decreased most in the HS-HES patients (−44%) and was lowest after CPS in these patients. Laser Doppler flow was most increased in the HS-HES patients before as well as after CPS. It is concluded that both kinds of volume given before CPS resulted in an improvement in hemodynamics into the postbypass period. Infusion of HSHES led to the most improved systemic and microcirculatory perfusion, which cannot be explained by the endocrinologic response alone.

We studied 15 patients undergoing cardiopulmonary bypass (CPB) to examine the effect of response to correction of acidosis on microcirculatory blood flow. Acidosis was defined when base excess was less than -10.0 mmol litre-1 while carbon dioxide partial pressure was within the normal range. CPB was carried out at almost normothermic temperature (smallest rectal temperature 35.2 (SD) 0.4 degrees C). Sodium bicarbonate (NaHCO3) was given to correct acidosis during steady state CPB. Skin microcirculatory blood flow was assessed using a double-channel laser Doppler flow (LDF) monitor. LDF was measured on the patient's forehead and forearm before infusion of NaHCO3 (baseline) and 30 s, 1, 3, 5, 7, 10 and 15 min later. Skin, blood, rectal and nasopharyngeal temperatures did not change during the investigation. Plasma viscosity, haemoglobin and carbon dioxide partial pressure also remained unchanged. Mean arterial pressure (MAP) and systemic vascular resistance (SVR) decreased slightly after infusion of NaHCO3 (MAP -29%; SVR -32%). A total of NaHCO3 99.4 (4.4) mmol litre-1 was given for correction of acidosis. pH and HCO3- were within the normal range shortly after the infusion of NaHCO3. LDF measured on both the forehead (+49%) and the forearm (+29%) increased significantly after infusion of NaHCO3. Changes in pH correlated positively with changes in LDF (analyses of co-variance, P < 0.02), but haemodynamic and other laboratory values did not correlate with LDF. We conclude that the microcirculatory response to correction of acidosis with NaHCO3 during CPB can be monitored using skin laser Doppler flowmetry. Infusion of NaHCO3 resulted in a significant improvement in skin microcirculatory perfusion.

The introduction of the pulmonary artery (PA) catheter in routine practice by Swan and Ganz at the beginning of the 1970s has enhanced our understanding of the mechanisms of patients' decompensation and has helped to guide appropriate therapeutic interventions in many diseases. Everybody who uses this monitoring instrument should become familiar with its technical concepts and theoretical basis. Modern technology has provided a large number of sophisticated developments, particularly in the past decade. Today we are able to obtain a huge mass of haemodynamic and oxymetric data in the critically ill. It is a common misconception in clinical practice that PA catheters should be employed for documentation of the haemodynamic catastrophe; however, it should be used to avoid significant haemodynamic problems. In recent years the value of PA catheter monitoring has been called into question. Whether a monitoring device can improve 'outcome' may be doubted. Although some opponents of haemodynamic monitoring wish to turn back the clock to the old days of a 'finger on the pulse', there is no doubt that the use of the PA catheter may yield additional information or that some of this information may be useful when the data are interpreted carefully. The time has come not only to criticize this monitoring instrument, but to examine future perspectives and visions.

Pharmacological support is often required during and after weaning from cardiopulmonary bypass. Most standard therapy acts on alpha-, beta- or dopaminergic-receptors, but down-regulation of beta-receptors has led to the development of agents which act independently from the beta-receptor. The phosphodiesterase (PDE) III inhibitor enoximone, was evaluated in cardiac surgery. Application of enoximone prior to weaning from CPB improved overall cardiac function, reduced the need for catecholaminergic inotropic support, and provided increased organ perfusion even 2 h after the operation. 'Pre-treatment' with enoximone may be beneficial, due to its ability to combine inotropic support with systemic and pulmonary vasodilatation, and may be considered as a first-line approach instead of catecholamines.

In 30 consecutive children undergoing cardiac surgery, two different types of fluid were given randomly for volume replacement in the pre-bypass period. In group 1 (n = 15), low molecular weight hydroxyethyl starch solution (LMW-HES) (6% HES; mean molecular weight 200,000 Da, molar substitution 0.5) and in group 2 (n = 15) 20% albumin (HA) was infused from the induction of anaesthesia until the start of cardiopulmonary bypass (CPB). In addition to haemodynamic values, various laboratory variables were measured before and after CPB until the morning of the 1st day after operation. The patients did not differ in diagnosis and conduct of CPB (lowest rectal temperatures: group 1 29.0 (SD 1.1) degrees C; group 2 29.4 (1.0) degrees C). Haemodynamic data (MAP, HR, CVP), anti-thrombin-III, fibrinogen, platelet count and coagulation variables were comparable between the groups until the 1st day after operation. Postoperative blood loss and the use of homologous blood or blood products were similar in all children. Albumin concentration increased after infusion of albumin (35-47 g litre-1) and was significantly greater until the end of the operation compared with the LMW-HES-treated children. Colloid osmotic pressure, however, was similar in the two groups and returned to baseline values on the 1st day after operation (LMW-HES group 19.31 (1.2) mm Hg; HA group 18.0 (1.3) mm Hg). Post-bypass urine output and creatinine values also did not differ between the groups. Anaphylactic reactions were not observed in any of the patients. It can be concluded that LMW-HES solution can be used effectively and safely for volume replacement in the pre-bypass period in small children undergoing cardiac surgery.

The ideal solution for volume therapy is still under discussion. In cardiac surgery, hemodynamic efficacy as well as the influence of cardiopulmonary bypass (CPB) are of major interest when administering volume. Hypertonic sodium (HS) solutions which have been advocated for resuscitation from hemorrhagic shock may also be of benefit in cardiac surgery patients. Hypertonic saline solution (7.5%) prepared in 6% hydroxyethyl starch solution (HS-HES) were infused in patients undergoing aortocoronary bypass grafting to double reduced baseline pulmonary capillary wedge pressure (PCWP < 4 mmHg). Volume replacement was carried out before (within 15 min), during (within 2 min), and after CPB (within 15 min). Significantly less HS-HES solution than standard 6% HES solution was necessary to double baseline PCWP. Cardiac index (CI) increased more and systemic vascular resistance (SVR) decreased more pronounced in the HS-HES group than in the 6% HES-patients. Fluid requirements in the patients having received hypertonic solution preoperatively were significantly less during CPB. Pulmonary function (paO2, Qs/Qt) was less changed in the HS-HES patients indicating avoidance of (interstitial) fluid overload in these patients. Infusion of HS-HES after weaning from CPB resulted in overall more improved hemodynamics than volume replacement with 6% HES. Rapid infusion of HS-HES during CPB (within 2 min) was followed by a significant, but shortlasting decrease in MAP (-40 mm Hg) and an increase in the oxygenator volume. Preoperative infusion of HS-HES resulted in a significant improvement in skin capillary microcirculation assessed by lased Doppler technique during and after CPB.(ABSTRACT TRUNCATED AT 250 WORDS)