Ralf Huth

Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version.

In 2010, under the guidance of the DGAI (German Society of Anaesthesiology and Intensive Care Medicine) and DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), twelve German medical societies published the “Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium in Intensive Care”. Since then, several new studies and publications have considerably increased the body of evidence, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) from 2013. For this update, a major restructuring and extension of the guidelines were needed in order to cover new aspects of treatment, such as sleep and anxiety management. The literature was systematically searched and evaluated using the criteria of the Oxford Center of Evidence Based Medicine. The body of evidence used to formulate these recommendations was reviewed and approved by representatives of 17 national societies. Three grades of recommendation were used as follows: Grade “A” (strong recommendation), Grade “B” (recommendation) and Grade “0” (open recommendation). The result is a comprehensive, interdisciplinary, evidence and consensus-based set of level 3 guidelines. This publication was designed for all ICU professionals, and takes into account all critically ill patient populations. It represents a guide to symptom-oriented prevention, diagnosis, and treatment of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine.

Reduced inotropic support after aprotinin therapy during pediatric cardiac operations

BACKGROUND Several reports indicate that aprotinin treatment before and during cardiopulmonary bypass (CPB) might have a protective effect on the myocardium. We evaluated the hemodynamic effects of perioperative aprotinin treatment. METHODS We conducted a randomized, double-blind, placebo-controlled trial in 34 infants (mean age, 2.5 years) who had cardiac operations. Half of the patients received high-dose aprotinin therapy. There were no significant differences between the aprotinin and placebo groups with respect to age, weight, sex, aortic cross-clamp time, and CPB time. The following data were recorded at arrival in the intensive care unit 6, 12, 24, and 48 hours after termination of CPB: heart rate, blood pressure, left atrial pressure, central-peripheral temperature difference, arterial-central venous oxygen saturation difference, urine output, serum creatinine, lactate and neutrophil elastase levels, the Doppler echocardiographic factors shortening fraction and preejection period/left-ventricular ejection time, and cumulative doses of catecholamines (epinephrine), enoximone, and furosemide. RESULTS No hemodynamic variable showed any significant difference between aprotinin and placebo groups. Urine output, creatinine, lactate, and elastase levels, as well as the cumulative doses of furosemide and epinephrine were not significantly different. Twelve hours after CPB 10 patients in the placebo group and 4 in the aprotinin group had received enoximone (p<0.05). The placebo group had received significantly larger doses of enoximone than the aprotinin group at arrival in the intensive care unit (0.13+/-0.05 versus 0 mg/kg), 12 hours after CPB (0.58+/-0.14 versus 0.18+/-0.09 mg/kg), 24 hours after CPB (1.11+/-0.24 versus 0.42+/-0.16 mg/kg), and 48 hours after CPB (1.61+/-0.40 versus 0.86+/-0.28). At 6 hours the difference did not reach statistical significance. CONCLUSIONS Clinical and hemodynamic status of the aprotinin-treated patients was similar to that of the placebo-treated patients in the first 48 hours after CPB. The placebo group, however, required significantly more inotropic support by enoximone than the aprotinin group to achieve this goal.

Continuous measurement of cardiac output by the Fick principle in infants and children: Comparison with the thermodilution method

ObjectiveTo compare a system that continuously monitors cardiac output by the Fick principle with measurements by the thermodilution technique in pediatric patients.DesignProspective direct comparison of the above two techniques.SettingPediatric intensive care unit of a university hospital.Patients25 infants and children, aged 1 week to 17 years (median 10 months), who had undergone open heart surgery were studied. Only patients without an endotracheal tube leak and without a residual shunt were included.MethodsThe system based on the Fick principle uses measurements of oxygen consumption taken by a metabolic monitor and of arterial and mixed venous oxygen saturation taken by pulse- and fiberoptic oximetry to calculate cardiac output every 20 s.InterventionsIn every patient one pair of measurements was taken. Continuous Fick and thermodilution cardiac output measurements were performed simultaneously, with the examiners remaining ignorant of the results of the other method.ResultsCardiac output measurements ranged from 0.21 to 4.55 l/min. A good correlation coefficient was found:r2=0.98;P<0.001; SEE=0.14 l/min. The bias is absolute values and in percent of average cardiac output was −0.05 l/min or −4.4% with a precision of 0.32 l/ min or 21.3% at 2 SD, respectively. The difference was most marked in a neonate with low cardiac output.ConclusionContinuous measurement of cardiac output by the Fick principle offers a convenient method for the hemodynamic monitoring of unstable infants and children.

Effects of dobutamine on left ventricular performance in newborns as determined by systolic time intervals

To evaluate the effects of dobutamine on myocardial function in newborns, left ventricular systolic time intervals (STI) — normalized pre-ejection period (PEPI), normalized left ventricular ejection time (LVETI) and pre-ejection period to left ventricular ejection time ratio (PEP/LVET) — were assessed by echocardiography in 18 newborns treated with dobutamine for clinically diagnosed heart failure. Examinations were performed prior to and 30 min after starting dobutamine infusion (7.5 or 10 μg/kg per min). Patients were assigned to two groups according to their PEP/LVET prior to dobutamine administration: group I (n=9) with pre-treatment PEP/LVET ≤ 0.35 and group II (n=9) with pre-treatment PEP/LVET > 0.35. While there was no change of STI in group I, dobutamine infusion resulted in a significant decrease in PEPI (from 102±4.8 to 87.8±4.2; mean ± SEM;P<0.01) and of PEP/LVET (from 0.56±0.05 to 0.45±0.05; mean ±SEM;P<0.01) and in a significant increase of LVETI (from 237.6±5.6 to 253.3±5.2; mean ±SEM;P<0.01) in group II. Heart rate increased significantly in both groups. Left ventricular end-diastolic dimension, also assessed by echocardiography, did not change in the eight studies performed. An increase in mean arterial pressure was found in three out of five newborns of group II and in one out of four patients in group I. It is concluded that dobutamine can improve cardiac performance in newborns with impaired left venfricular function. This effect is probably due to an improvement in myocardial contractility.

A novel approach for selective brain cooling: implications for hypercapnia and seizure activity

ObjectiveDuring selective brain cooling (SBC) the brain temperature (TB) is reduced while the core temperature (TC) remains unchanged. This animal study investigated changes in brain temperature induced by a novel approach of cooling the brain from the pharynx (pSBC) and whether these temperature changes are related to commonly encountered clinical situations (i.e., seizure activity and hypercapnia).DesignExperimental animal study.SubjectsMale Sprague-Dawley rats.InterventionspSBC was achieved by a heat exchanger placed in the pharynx; hypercapnia and seizure activity were induced by adding CO2 to the respiratory gases and by intravenous injection of bicuculline, respectively.Measurements and resultsTB, TC, and pharynx (TP) were measured continuously with thermocouples. During pSBC TB declined significantly from 36.9±0.67°C to 33.1±1.23°C. There was a trend towards lower TC during pSBC (from 36.9±0.70 to 36.4±1.2°C). TP during pSBC was 29.1±2.19°C. From the lowest achieved pSBC temperature TB rose during CO2 challenge by 1.22±0.67°C (vs. 0.85±0.34°C in non-SBC controls). From the lowest pSBC temperature during seizure activity TB rose by 2.08±0.35°C (vs. 1.15±0.55°C in non-SBC controls).ConclusionsSignificant cooling of the cortex can be achieved by pSBC in a rat rodent model. Marked increases in TB with hypercapnia and with seizure activity were observed. These results may have implications for cooling methods in clinical settings. For example, pSBC may offer distinct advantages over alternative methods such as whole-body cooling and externally implemented SBC.

Effects of tolazoline and prostacyclin on pulmonary hypertension in infants after cardiac surgery

OBJECTIVE To evaluate the hemodynamic effects of tolazoline and prostacyclin in infants with pulmonary vasospasm after cardiac surgery. DESIGN Prospective cohort study. SETTING Pediatric ICU. PATIENTS The cohort consisted of 42 infants and children with congenital heart disease and pulmonary hypertension who underwent corrective surgery and were monitored postoperatively using pulmonary artery catheters. Fourteen infants (2 to 12 months old) in this group required postoperative treatment with tolazoline or prostacyclin. INTERVENTIONS Tolazoline was administered as a bolus of 0.5 mg/kg for treatment of persistent pulmonary hypertension or acute pulmonary hypertensive crisis. If its effectiveness was proved after 30 mins by hemodynamic measurements, a continuous iv infusion of 0.5 mg/kg/hr was established. Higher doses of tolazoline were avoided. If tolazoline treatment did not fulfill the criteria for pulmonary vasodilation, prostacyclin was given by continuous iv infusion at a starting rate of 5 ng/kg/min, followed by 10 ng/kg/min. In three patients, the infusion rate was increased to 15 ng/kg/min. RESULTS Bolus administration of tolazoline resulted in a distinct pulmonary vasodilation in seven infants: mean pulmonary artery pressure and pulmonary vascular resistance decreased by an average of 35% and 45%, respectively. In these patients, tolazoline was infused over the following 12 to 72 hrs. One infant who received tolazoline for 72 hrs developed a clinically important gastrointestinal hemorrhage. In seven nonresponders to tolazoline, prostacyclin (PGI2) at an infusion rate of 5 ng/kg/min led to pulmonary vasodilation in five patients, at an iv infusion rate of 10 ng/kg/min in all seven infants studied. The latter dose of PGI2 reduced the mean pulmonary artery pressure by an average of 37%, and pulmonary vascular resistance by 43%. Transient withdrawal of prostacyclin in five infants demonstrated its short half-life and clinical effectiveness. Apart from a facial flush, no side-effects were encountered using PGI2 as an infusion over durations ranging from 12 to 504 hrs. CONCLUSIONS These data suggest that, if tolazoline in a relatively low dose proves to be inefficient, prostacyclin can still be used as a safe and effective drug for treatment of pulmonary vasospasm. Prostacyclin offers more than a pharmacologic alternative to increased tolazoline dosages.

Continuous monitoring of mixed venous oxygen saturation in infants after cardiac surgery

Continuous mixed venous oxygen saturation SvO2c was measured in 16 infants immediately after cardiac surgery. A polyurethane 4F, dual channel catheter (Opticath, Modell U440, Oximetrix) with fiberoptic filaments was introduced into the pulmonary artery during cardiothoracic surgery. The catheters were left in place for an average of 67.5 h (range 27 h – 125 h) and there were no catheter-related complications. Correlation between continuous in vivo SvO2 values and in vitro values was satisfactory (r=0.85), whereas a correlation between SvO2c and arterial oxygen saturation (SaO2) was not found (r=0.07). The sampled arterial lactate values were inversely correlated to the simultaneously measured SvO2c, but the corelation coefficient was only r=-0.4. There was an inverse correlation between SvO2c and arteriovenous oxygen content difference (Ca−vDO2c) (r=-0.82), and a marked inverse correlation to the calculated oxygen utilization ratio (r=-0.97). Therefore SvO2c continuously reflects the overall balance between oxygen consumption and delivery, but the use of SvO2 as a predictor of blood lactate levels is unreliable. A further purpose of the present study was to demonstrate the clinical applications and to show the usefulness of SvO2c-monitoring; particularly as a surveillance and early warning system, as a guide for assessing therapy and its relevance in interpreting other monitored parameters. In our opinion continuous SvO2 measurement is a reliable and valuable indicator of cardiopulmonary function in the immediate post-operative period, even in infants with complicated repair of cardiac malformations.

Nitric oxide and prostacyclin lower suprasystemic pulmonary hypertension after cardiopulmonary bypass

In a 3-week-old male newborn persistent suprasystemic pulmonary hypertension developed after surgical valvulotomy for a critical aortic valve stenosis. Because of a residual transvalvular pressure gradient of 35 mm Hg and postoperative left as well as right ventricular dysfunction, treatment with inhaled nitric oxide (NO) and intravenously infused prostacyclin (PGI2) was attempted. Low-dose inhaled NO and low dose PGI2 corrected severe pulmonary hypertension and led to an increase in cardiac output. Treatment with NO but not PGI2 was accompanied by a rise in PaO2 and systemic blood pressure. Interruption of NO administration led to a rapid increase in pulmonary arterial pressure to suprasystemic levels. With continued i.v. PGI2 and decreasing concentrations of NO, severe pulmonary hypertension resolved after a few days suggesting that a transient endothelial dysfunction was partially responsible for pulmonary vasoconstriction. NO inhalation appears to be an effective new tool in the treatment of severe pulmonary hypertension following cardiac surgery.

Complicated Nosocomial Pneumonia due to Legionella pneumophila in an Immunocompromised Child

An immunocompromised child developed necrotizing pneumonia with BAL cultures growing Legionella pneumophila resistant to treatment, including erythromycin and rifampicin. Ciprofloxacin and clarithromycin reversed the clinical course; their use as first-line drugs is justifiable and a high index of suspicion for the occurrence of legionellosis is warranted.

Successful treatment of a patient with ARDS after pneumonectomy using high-frequency oscillatory ventilation.

Abstract High frequency oscillatory ventilation (HFOV) was used in a patient who developed the acute respiratory distress syndrome 5 days following a right pneumonectomy for bronchogenic carcinoma. When conventional pressure-controlled ventilation failed to maintain adequate oxygenation, HFOV dramatically improved oxygenation within the first few hours of therapy. Pulmonary function and gas exchange recovered during a 10-day period of HFOV. No negative side effects were observed. Early use of HFOV may be a beneficial ventilation strategy for adults with acute pulmonary failure, even in the postoperative period after lung resection.