Retraction notice to "The role of enoximone in cardiac surgery" [Br J Anaesth 69 (1992) 45-50].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review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.

Retraction notice to "Volume replacement with hydroxyethyl starch solution in children" [Br J Anaesth 70 (1993) 661-5].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review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.

Retraction notice to "Does correction of acidosis influence microcirculatory blood flow during cardiopulmonary bypass?" [Br J Anaesth 71 (1993) 277-81].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review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.

Retraction notice to "Endothelial-related coagulation in cardiac surgery" [Br J Anaesth 74 (1995) 174-9].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review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.

Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on gas exchange and haemodynamics.

The aim of the present study was to investigate the feasibility and efficacy of bronchoscopic surfactant administration in a noncontrolled multicentre study in five university centres. A total number of 27 patients, suffering from severe acute respiratory distress syndrome (mean+/-SEM lung injury score: 3.15+/-0.06) and septic shock (Acute Physiology and Chronic Health Evaluation (APACHE) II score at study entry 33.2+/-1.3, lactate 4.3+/-0.6 mmol x L(-1)) were studied. The patients were ventilated with a mean tidal volume of 11.0+/-0.5 mL x kg(-1) body weight (bw), either volume or pressure controlled, with 16.3+/-2.8 cmH2O positive end-expiratory pressure, for an average of 3.5+/-0.3 days at study entry. A natural bovine surfactant extract (300 mg x kg(-1) bw Alveofact; mean total volume 378 mL) was delivered in divided doses to each segment of the lungs via flexible bronchoscope within approximately 45 min. No untoward effects on gas exchange, lung mechanics and haemodynamics were noted during the procedure of surfactant administration. Within 12 h the oxygen tension in arterial blood/inspiratory oxygen fraction increased from a mean of 109+/-8 mmHg to 210+/-20 mmHg (p<0.001). In seven patients, in whom gas exchange again deteriorated with further progression of the disease, a second surfactant dose of 200 mg x kg(-1) was administered 18-24 h after the first application, again improving arterial oxygenation. A total of 15 patients survived the 28-day study period (mortality rate 44.4%, compared to a calculated risk of death for the given APACHE II scores of 74.0+/-3.5%), with all causes of death being nonrespiratory. The bronchoscopic application of a high dose of natural surfactant in patients with severe acute respiratory distress syndrome and septic shock is both feasible and safe, resulting in a pronounced improvement in gas exchange.

[Ventilation according to the "open lung" concept of multiple trauma patients]. / Beatmung nach dem "open-lung"-Konzept bei polytraumatisierten Patienten.

OBJECTIVE: The ventilation mode clearly influences the course of patients with multiple trauma on the ICU. Ventilation according the "open lung" approach rapidly opens up atelectatic lung regions. Generation of an adequate intrinsic PEEP enables to keep the lung open. We studied the consequences of the "open lung" approach on the lung function and monitored its side effects on patients with multiple trauma. METHODS: 18 consecutive patients with multiple trauma and additional thoracic trauma were routinely ventilated according the "open lung" approach between May and November 1999. We were mainly interested in data of lung mechanics, oxygenation and ventilation. Side effects on other organ systems and consequence for the infection rate were monitored. RESULTS: Ventilation according the "open lung" approach enables early sufficient oxygenation and ventilation of patients with severe multiple trauma and accompanying thoracic trauma. The ventilation mode helps to prevent baro-, volu- and atelectrauma and thus fulfils the requirements for a present-day ventilation mode. An immediate complete healing of the lung damages was not found. Nevertheless, as a trend the length of ventilation support seems short. Even extensive osteosynthesis at multiple fractures was possible without delay. Side effects of the high opening pressure on the lung or other organs as well as sequels of the high intrinsic PEEP on liver, kidney or intestine were not found. The infection rate was low, therapeutic doses of antibiotics were necessary only in less than half of the ICU-stay. CONCLUSION: Ventilation according the "open lung" approach is a very effective and safe way to ventilate patients after severe multiple trauma with accompanying thoracic trauma.

Thrombin generation and activation of the thrombomodulin protein C system in open heart surgery depend on the underlying cardiac disease.

The exposure of blood to foreign surfaces during extracorporeal circulation (ECC) leads to an activation of the coagulation system. In arteriosclerotic patients thrombin activation is increased and plasma fibrinogen is elevated, while protein C levels are reduced. In this study we investigated the influence of different cardiac diseases on ECC-induced thrombin generation and activation of the thrombomodulin-protein C system. Twenty-four patients undergoing either elective coronary artery bypass grafting (CABG) or elective aortic valve replacement (AVR) were included in the study. Blood samples were taken at different time intervals before, during and after ECC, and in the postoperative period. Plasma concentrations of thrombin-antithrombin III-complex (TAT), modified antithrombin (ATM), prothrombin fragment F1+2, free protein S, thrombomodulin, and protein C-antigen were determined by ELISA. Fibrinogen and antithrombin III levels were detected by nephelometry. Both groups were comparable with respect to biometric and ECC-related data. TAT concentrations were elevated in both groups after induction and increased during surgery (p<0.001). As a marker of thrombin generation levels of F1+2 were higher in the CABG group during cardiopulmonary bypass (p=0.003). In CABG patients ATM peaks were higher during ECC (p=0.0024). Significantly higher plasma thrombomodulin concentrations were found in CABG patients after induction (p<0.001), while protein S concentrations were higher in the AVR group (p=0.002). Protein C levels and antithrombin III concentrations did not differ between the groups. Patients undergoing CABG were found to have lower protein S levels and increased plasma thrombomodulin concentrations as markers of endothelial damage. In these patients contact activation and as a consequence thrombin generation takes place at a higher level, indicating a hypercoagulable state. Thromboembolic events in the perioperative period may be caused by different hemostatic changes in CABG patients.

Extracorporeal circulation increases nitric oxide-induced methemoglobinemia in vivo and in vitro.

OBJECTIVES: Methemoglobinemia is a well-known side effect of nitric oxide inhalation. We tested the hypothesis whether cardiopulmonary bypass increases methemoglobin formation by nitric oxide. DESIGN: A two-phase study: a) a controlled, prospective in vivo study of inhaled nitric oxide treatment followed by b) a second, prospective and controlled in vitro study. SETTING: Pediatric intensive care unit and research laboratory in a university hospital. PATIENTS: The in vivo study consisted of 25 patients following open-heart surgery and 19 children with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn. The in vitro study consisted of 20 patients with and 20 patients without cardiopulmonary bypass. INTERVENTIONS: For the in vivo study, methemoglobin measurements were taken before and after application of 20 parts per million (ppm) of nitric oxide. For the in vitro study, red blood cells of patients were incubated with 32 ppm nitric oxide before and after surgery. Methemoglobin, glutathione, adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADHP) concentrations were compared. MEASUREMENTS AND MAIN RESULTS: For the in vivo study, nitric oxide inhalation increased methemoglobin from 0.2 +/- 0.1% to 1.2 +/- 0.7% in patients receiving nitric oxide after open-heart surgery and from 0.2 +/- 0.1% to 0.5 +/- 0.4% in ARDS/persistent pulmonary hypertension of the newborn patients (p < .01). For the in vitro study, nitric oxide incubation of red blood cells increased methemoglobin concentration from 3.7 +/- 1.9% preoperatively to 7.4 +/- 2.4% after open-heart surgery. This increase was not observed in patients who did not undergo cardiopulmonary bypass (3.6 +/- 1.6% vs. 3.6 +/- 1.9%; p < .001). In erythrocytes of patients undergoing extracorporeal circulation, there was no difference between pre- and postoperative glutathione, ATP, and NADH/NADPH concentrations. CONCLUSIONS: Cardiopulmonary bypass is an important risk factor for methemoglobinemia when inhaled nitric oxide is applied. This risk is not secondary to diminished concentrations of energetic substrates.

Perioperative management of pulmonary hypertension after heart transplantation in childhood.

BACKGROUND: Pulmonary hypertension is responsible for a substantial part of perioperative and postoperative mortality and morbidity after cardiac transplantation. Treatment of right ventricular failure after increased pulmonary vascular resistance is difficult especially in infants and children. Therefore we started a preventive therapy of pulmonary hypertension after cardiac transplantation to avoid right ventricular failure and compared the results with a group of patients with conventional therapy. METHODS: Group 1 (n = 13), with transplantation from 1988 to 1991, was treated with vasodilators when symptoms of right ventricular failure developed. Group 2 (n = 19) had preventive treatment with prostaglandin E1 (PGE1), the phosphodiesterase-III inhibitor enoximone, and alkalinazation starting during weaning from cardiopulmonary bypass. RESULTS: Six patients in group 1 died; four of them as the result of right ventricular failure in the immediate postoperative course despite aggressive treatment. In group 2 there were three deaths as the results of rejection (2) and infection (1). None of these patients developed right ventricular failure (p = 0.02). Cold ischemic time, extracorporeal circulation time, and waiting time before transplantation were significantly longer in group 2. Side effects of this preventive therapy were not observed. CONCLUSIONS: We conclude that prophylactic therapy of pulmonary hypertension with vasodilators in infants and children after heart transplantation is safe and effective in preventing right ventricular failure in the postoperative course.

Inhaled nitric oxide in neonatal and pediatric acute respiratory distress syndrome: dose response, prolonged inhalation, and weaning.

OBJECTIVE: Inhaled nitric oxide is a potent and selective pulmonary artery vasodilator. We studied the effects of nitric oxide inhalation in neonatal and pediatric acute respiratory distress syndrome (ARDS) patients with respect to dosage, prolonged inhalation, and weaning. DESIGN: Prospective, open-label study. SETTING: Neonatal and pediatric intensive care units of a level three university hospital. PATIENTS: Seventeen patients with severe ARDS (1 day to 6 yrs of age [mean 1.75]; oxygenation index of > 20 cm H2O/torr) were enrolled. INTERVENTIONS: To identify the optimal dosage for continuous nitric oxide inhalation, doses between 1 and 80 parts per million (ppm) of nitric oxide were tested after the patients had stabilized. Daily withdrawals of nitric oxide were made, according to predetermined criteria. MEASUREMENTS AND MAIN RESULTS: Nine neonatal and eight pediatric ARDS patients (mean Pediatric Risk of Mortality score 28.4 +/- 6.1; mortality risk 54 +/- 15%) were studied. The following variables changed within 24 hrs of nitric oxide inhalation: mean oxygenation index decreased by 56% (from 34 +/- 12 to 15 +/- 7 cm H2O/torr, p = .0004); alveolar-arterial O2 gradient decreased by 31% (from 579 +/- 71 to 399 +/- 102 torr (77.2 +/- 9.5 to 53.2 +/- 13.6 kPa), p = .0004); and mean systemic arterial pressure increased by 15% (from 49 +/- 10 to 57 +/- 12 mm Hg, p = .0029). The optimal dose of nitric oxide was 20 ppm in neonates (with additional persistent pulmonary hypertension of the newborn) and 10 ppm in pediatric patients. Prolonged inhalation (4 to 21 days) was associated with continuous improvement of oxygenation. An oxygenation index of < 5 cm H2O/torr predicted successful withdrawal, with a sensitivity of 75% and a specificity of 89%. None of the patients had to be rescued with extracorporeal membrane oxygenation and 16 of the 17 patients survived. CONCLUSIONS: Inhaled nitric oxide enhances pulmonary gas exchange, with concomitant hemodynamic stabilization, in neonatal and pediatric ARDS. Best effective doses were 10 ppm of nitric oxide in pediatric ARDS and 20 ppm in neonates. Treatment should be continued until an oxygenation index of < or = 5 cm H2O/torr is achieved. Effects on outcome need verification in larger controlled trials.

Changes in heart rate variability during induction of anesthesia with fentanyl and midazolam.

OBJECTIVE: The study was designed to evaluate changes in autonomic nervous system function during induction of anesthesia with fentanyl, midazolam, and pancuronium and to answer the question of dose-dependency of these effects. DESIGN: Prospective, randomized. SETTING: A university hospital. PARTICIPANTS: Forty consecutive cardiac surgical patients. INTERVENTIONS: Anesthesia was induced with fentanyl, midazolam, and pancuronium. The patients were assigned to four groups differing in dosages of fentanyl plus midazolam and speed of injection. Fentanyl, 7.5 micrograms/kg (group A), 12.5 micrograms/kg (group B), and 20.0 micrograms/kg (group C) plus midazolam, 0.075 mg/kg (group A), 0.125 mg/kg (group B), and 0.200 mg/kg (group C) were administered over 10 minutes; in group D, fentanyl, 7.5 micrograms/kg, and midazolam, 0.075 mg/kg, were administered within 1 minute. MEASUREMENTS AND MAIN RESULTS: Heart rate variability (HRV) was measured using parameters in the time domain and the frequency domain. The comparison of preinduction HRV with the intra-anesthetic epochs did not show significant differences with respect to heart rate, coefficient of variation, and root mean squared successive differences. Spectral analysis showed significant reductions of power in the vasomotor band (0.01 to 0.05 Hz) and the low-frequency band (0.05 to 0.15 Hz) in all groups. Power in the high-frequency band (0.15 to 0.50 Hz) decreased slightly, but this did not reach the significance level. A dose dependency of these changes was found in the low-frequency band only. CONCLUSIONS: Parameters of HRV suggest that induction with fentanyl, midazolam, and pancuronium decreases sympathetic but not parasympathetic autonomic system activity. The anesthetic induction technique's modulation of autonomic nervous system balance is better represented by means of spectral analysis than by analysis in the time domain. This modulation was largely independent of the doses administered and independent of the speed of injection.

Comparison of different prophylactic myocardium saving measures during heart surgery. Effects on perioperative troponin-T levels.

OBJECTIVE: Different prophylactic myocardium saving strategies are often routine in open heart surgery. Even if theoretically well established, they must be critically reviewed in times of limited financial resources. EXPERIMENTAL DESIGN: Troponin-T (TnT) is a valuable tool to detect even minor myocardial damages independently from concomitant muscle injuries. We measured intra- and postoperative TnT-values and ST-wave deviations on the ECG in a control group and in patients receiving one of the following prophylactic MEASURES: hypothermia during cardiopulmonary bypass (CPB), nitroglycerine ([0.5 microgram/kg/min]) or nifedipine [0.1 microgram/kg/min] after aortic cross-clamping until end of operation, or perioperative Mg2+ per os. PATIENTS AND SETTING: The study included 65 patients of a university hospital with preoperative good heart function scheduled for elective aorto-coronary bypass operation. RESULTS: TnT values increased in all groups after CPB and peaked between end of operation and first post-operative day. TnT values above the critical border of 1.0 microgram/l in the early period after CPB were less often seen in the nitroglycerine and nifedipine group. No pronounced differences could be observed after the first postoperative day. Patients of the hypothermia group had most often TnT values above 1.0 microgram/l. Maximum TnT values of the control, the hypothermia and the Mg(2+)-group correlated with the duration of aortic-crossclamping. No correlation existed between ST-deviations and TnT-values. CONCLUSIONS: The prophylactic measures failed to reduce myocardial damage as evidenced by the course of TnT values. They can therefore not be recommended as routine strategies in patients with good left heart function. Especially hypothermia should be considered carefully.

Normothermic versus hypothermic cardiopulmonary bypass: do changes in coagulation differ?

BACKGROUND: The differences between hypothermic and normothermic cardiopulmonary bypass (CPB) on platelet function and endothelial-related coagulation (eg, the thrombomodulin/protein C/protein S system) should be investigated. METHODS: According to a randomized sequence, 30 patients undergoing aortocoronary bypass grafting underwent either hypothermic (rectal temperature, 27 degrees C to 28 degrees C, n = 15) or normothermic CPB (rectal temperature, more than 35 degrees C, n = 15). Arterial blood samples were taken after induction of anesthesia (baseline values), before, during, and immediately after CPB, 5 hours after CPB, and on the morning of the first postoperative day. Circulating thrombomodulin, (free) protein S, protein C, and thrombin/antithrombin III complex were measured from these samples. Platelet function was assessed by aggregometry (turbidometric technique) induced by adenosine diphosphate (2 mumol/L), collagen (4 micrograms/L), and epinephrine (25 mumol/L). RESULTS: Hypothermic patients showed a significantly higher blood loss and need for homologous blood than the normothermic patients. Thrombomodulin plasma level increased more in the hypothermic (from 28 +/- 5 ng/mL to 60 +/- 10 ng/mL) than in the normothermic group (from 28 +/- 7 ng/mL to 41 ng/mL); p < 0.05). Both protein C and (free) protein S were reduced significantly in the hypothermic (protein C, from 88% +/- 25% to 60% +/- 11%; protein S, from 71% +/- 10% to 40% +/- 8%) than in the normothermic patients. Platelet aggregation was significantly more decreased in the hypothermic (adenosine diphosphate, maximum decrease by -43% relative to baseline) than in the normothermic patients (adenosine diphosphate, maximum decrease by -22% relative to baseline). In the hypothermic CPB group, platelet aggregation had recovered incompletely, whereas in the normothermic patients platelet aggregation even slightly exceeded baseline values. CONCLUSIONS: Hypothermic CPB resulted in more pronounced alterations of platelet aggregation and endothelial-related coagulation than normothermic CPB. Plasma levels of soluble thrombomodulin were more increased in hypothermic than in normothermic CPB indicating more extensive endothelial damage or activation associated with hypothermic CPB.

[NO inhalation in heart surgery procedures: relevance for right heart function?]. / NO-Inhalation bei herzchirurgischen Eingriffen: Relevanz für die Rechtsherzfunktion?

UNLABELLED: The right ventricle is more jeopardized by a cardiopulmonary bypass than the left one. Impaired right ventricular performance may profit from an afterload reduction. A selective reduction in pulmonary artery pressure (PAP) or pulmonary vascular resistance (PVR) without impairment of the systemic circulation seems to be possible by inhalation of nitric oxide (NO). Therefore in the present study we looked for influences of NO inhalation on PAP, PVR and right heart parameters immediately after weaning from the bypass. The dependence of endothelial function on age, preoperative heart function and extracorporeal circulation is well established. The relevance of such parameters on NO inhalation was also investigated. METHODS: After ethical approval and informed consent were obtained, 20 patients with moderately increased PAP were included in the study. Ten patients inhaled NO at a concentration of 30 ppm; the other group served as a control group. Measurement points were 10 min after the end of extracorporeal circulation (baseline), 3, 10, and 20 min after the start, as well as 10 min after the end of NO inhalation. NO was injected near the tube into the tubing system during inspiration; dosage and monitoring of the concentration were achieved by means of a chemiluminometer. Measured parameters consisted of PAP, PVR, right ventricular ejection fraction and volumes, systemic blood pressure and resistance, central venous pressure, pulmonary capillary wedge pressure, and oxygenation parameters (paO2, pvO2, paCO2). RESULTS: The decrease in PAP (from 29.7 +/- 3.9 to a minimal 25.4 +/- 4.3 mm Hg, P < 0.005) and in PVR (from 169.4 +/- 51.9 to a minimal 116.3 +/- 60.9 dyn.s.cm-5, P.0.05) did not improve right heart function. A similar significant increase in SVR was observed in the NO group and in the control group. Age, haemodynamic parameters or duration of the ischaemic phase of the cardiopulmonary bypass did not influence the course of PAP or PVR. Changes in PAP (from 30.0 +/- 4.0 to a minimal 26.7 +/- 3.6 mm Hg, P < 0.05) and PVR (from 149.0 +/- 41.5 to a minimal 125.2 +/- 51.5 dyn.s.cm-5, in the control group were not statistically different from those in the NO group. Indicators of intoxication like an increase in NO2 or methaemoglobin concentrations or changes in compliance or resistance were not observed. CONCLUSIONS: Patients with moderate pulmonary hypertension did not profit from NO inhalation immediately after weaning from the cardiopulmonary bypass. The decreases in PAP and PVR found in the NO or control group did not improve right-heart function. When the NO and control group were compared, specific effects of NO inhalation on PAP and PVR must be questioned. This could perhaps be explained by data from animal experiments, which found high endogenous NO levels in situations with elevated cytokine levels. Cytokines are increased after extracorporeal circulation. Oxygenation was not impaired by inhalation of relatively high concentrations of NO. For all investigations with NO inhalation not preceded by steady-state conditions, a control group is recommended.