Willehad Boemke

Key Performance Indicators in Intensive Care Medicine. A Retrospective Matched Cohort Study

Expert panel consensus was used to develop evidence-based process indicators that were independent risk factors for the main clinical outcome parameters of length of stay in the intensive care unit (ICU) and mortality. In a retrospective, matched data analysis of patients from five ICUs at a tertiary university hospital, agreed process indicators (sedation monitoring, pain monitoring, mean arterial pressure [MAP] ≥ 60 mmHg, tidal volume [TV] ≤ 6 ml/kg body weight, peak inspiratory pressure [PIP] ≤ 35 cmH2O and blood glucose [BG] ≥ 80 and ≤ 130 mg/dl) were validated using a prospective dataset of 4445 consecutive patients. After matching for age, sex and ICU, 634 patients were analysed. Logistic regression of the 634 patients showed that monitoring analgesia and sedation, MAP ≥ 60 mmHg and BG ≥ 80 mg/dl were relevant for survival. Linear regression of the 634 patients showed that analgesia monitoring, PIP ≤ 35 cmH2O and TV ≤ 6 ml/kg were associated with reduced length of ICU stay. Linear regression on all 4445 patients showed analgesia, sedation monitoring, MAP ≥ 60 mmHg, BG ≥ 80 mg/dl and ≤ 130 mg/dl, PIP ≤ 35 cmH2O and TV ≤ 6 ml/kg were associated with reduced length of ICU stay, indicating that adherence to evidence-based key process indicators may reduce mortality and length of ICU stay.

PREVENTION OF CATHETER-RELATED INFECTIONS BY A NEW, CATHETER-RESTRICTED ANTIBIOTIC FILLING TECHNIQUE

Catheter-related infections pose a hazard to both humans and laboratory animals. The aim of this study was to develop a technique preventing bacterial colonization of intravascular catheters. In 27 dogs a total of 70 catheters were implanted. On an average catheters were used for 207 days. Three protocols were compared: (1) flushing the catheters with a heparinized solution; (2) filling only the catheter lumen with α-ctchymotrypsin solution (225 units/ml); (3) filling only the catheter lumen with a solution containing a mixture of the aminoglycoside antibiotic gentamicin (20 mg/ml) and chymotrypsin (225 units/ml). Catheter fillings were always withdrawn before catheter use. Catheter exit sites were all treated with povidone iodine ointment once a day. Body temperatures and weights were recorded, bacteriological and electron microscopical examinations of catheters performed. Without gentamicin filling all catheters were colonized after a few weeks. The dogs showed clinical signs of chronic bacteraemia. Gentamicin filling eradicated colonization. No further bacteraemia was observed. We conclude that filling only the catheter lumen with a concentrated solution of chymotrypsin and gentamicin, combined with measures to prevent infections via the subcutaneous catheter tunnel, is an effective and safe technique to prevent catheter-related infections.

Referral practices in patients suffering from non-malignant chronic pain.

This paper presents the results of a prospective observational cohort study investigating referral practices to six specialized pain centres (SPCs) in 303 patients with headache (HD), low back pain (LBP), and neuropathic pain (NP). The study was divided into three parts. Part 1: The pain health care history (contacts with general practitioners and specialists, further referrals, time spans, therapies) before first contact with the SPC. Part 2: Reality of pain therapy and management in the SPC (patients’ attrition, interdisciplinarity of therapy and novel therapeutic strategies instigated). Part 3: Follow‐up and assessment of pain levels (NRS, SES), disability scores (PDI), QoL scores (SF 12), and anxiety and depression scores (HADS) at 0, 6 and 12 months. Using an ordinal linear regression model, factors predicting a good treatment outcome were identified.

Prone position during ECMO is safe and improves oxygenation

Purpose Combination of prone positioning (PrP) and extracorporeal membrane oxygenation (ECMO) might be beneficial in severe acute respiratory distress syndrome (ARDS), because both approaches are recommended. However, PrP during ECMO might be associated with complications such as dislocation of ECMO cannulae. We investigated complications and change of oxygenation effects of PrP during ECMO to identify “responders” and discuss our results considering different definitions of response in the literature. Methods Retrospective analysis of complications, gas exchange, and invasiveness of mechanical ventilation during first and second PrP on ECMO at specified time points (before, during, and after PrP). We used multivariate nonparametric analysis of longitudinal data (MANOVA) to compare changes of mechanical ventilation and hemodynamics associated with the first and second procedures. Results In 12 ECMO patients, 74 PrPs were performed (median ECMO duration: 10 days (IQR: 6.315.5 days)). No dislocations of intravascular catheters/cannulae, endotracheal tubes or chest tubes were observed. Two PrPs had to be interrupted (endotracheal tube obstruction, acute pulmonary embolism). PaO2/FiO2-ratio increased associated with the first and second PrP (p = 0.002) and lasted after PrP in 58% of these turning procedures (“responders”) without changes in ECMO blood flow, respiratory pressures, minute ventilation, portion of spontaneously triggered breathing, and compliance. Hemodynamics did not change with exception of increased mean pulmonary arterial pressure during PrP and decrease after PrP p≤0.001), while norepinephrine dosage decreased (p = 0.03) (MANOVA). Conclusions Prone position during ECMO is safe and improves oxygenation even after repositioning. This might ameliorate hypoxemia and reduce the harm from mechanical ventilation.

Sodium Nitrite Mitigates Ventilator-induced Lung Injury in Rats

Background: Nitrite (NO2 −) is a physiologic source of nitric oxide and protects against ischemia-reperfusion injuries. We hypothesized that nitrite would be protective in a rat model of ventilator-induced lung injury and sought to determine if nitrite protection is mediated by enzymic catalytic reduction to nitric oxide. Methods: Rats were anesthetized and mechanically ventilated. Group 1 had low tidal volume ventilation (LVT) (6 ml/kg and 2 cm H2O positive end-expiratory pressure; n = 10); group 2 had high tidal volume ventilation (HVT) (2 h of 35 cm H2O inspiratory peak pressure and 0 cm H2O positive end-expiratory pressure; n = 14); groups 3–5: HVT with sodium nitrite (NaNO2) pretreatment (0.25, 2.5, 25 &mgr;mol/kg IV; n = 6–8); group 6: HVT + NaNO2 + nitric oxide scavenger 2-(4-carboxyphenyl)-4,5dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3oxide(n = 6); group 7: HVT + NaNO2 + nitric oxide synthase inhibitor N&ohgr;-nitro-L-arginine methyl ester (n = 7); and group 8: HVT + NaNO2 + xanthine oxidoreductase inhibitor allopurinol (n = 6). Injury assessment included physiologic measurements (gas exchange, lung compliance, lung edema formation, vascular perfusion pressures) with histologic and biochemical correlates of lung injury and protection. Results: Injurious ventilation caused statistically significant injury in untreated animals. NaNO2 pretreatment mitigated the gas exchange deterioration, lung edema formation, and histologic injury with maximal protection at 2.5 &mgr;mol/kg. Decreasing nitric oxide bioavailability by nitric oxide scavenging, nitric oxide synthase inhibition, or xanthine oxidoreductase inhibition abolished the protection by NaNO2. Conclusions: Nitrite confers protection against ventilator-induced lung injury in rats. Catalytic reduction to nitric oxide and mitigation of ventilator-induced lung injury is dependent on both xanthine oxidoreductase and nitric oxide synthases.

ACE inhibition does not exaggerate the blood pressure decrease in the early phase of spinal anaesthesia

Background:  This study investigates whether long‐term treatment with an angiotensin converting enzyme inhibitor (ACEI) impairs the hemodynamic regulation during the early phase of spinal anaesthesia.

The haemodynamic and catecholamine response to xenon/remifentanil anaesthesia in Beagle dogs

The noble gas xenon seems to have minimal cardiovascular side-effects and so may be an ideal anaesthetic agent when investigating cardiovascular physiology. In comparison with standard modern anaesthetics, we investigated the haemodynamic and hormonal effects of xenon in Beagle dogs. After a 30 min baseline period, anaesthesia was induced with propofol and maintained with either (1) 1.2% isoflurane/70% nitrous oxide (N2O), (2) 0.8% isoflurane/0.5 µg/kg/min remifentanil or (3) 63% xenon/0.5 µg/kg/min remifentanil (n = 6 per group). Haemodynamics were recorded and blood samples taken before and 60 min after induction. Mean arterial blood pressure (MAP) was higher in conscious dogs than during isoflurane/N2O (86 ± 2 vs. 65 ± 2 mmHg, mean ± SEM) and isoflurane/remifentanil anaesthesia (95 ± 2 vs. 67 ± 3 mmHg), whereas MAP did not decrease significantly in response to xenon/remifentanil anaesthesia (96 ± 4 vs. 85 ± 6 mmHg). Bradycardia was present during isoflurane/remifentanil (54 ± 2/min) and xenon/remifentanil (40 ± 3/min), but not during isoflurane/N2O anaesthesia (98 ± 3/min, P < 0.05). Xenon/remifentanil anaesthesia induced the highest reduction in cardiac output (CO) (–61%), and the highest increase in systemic vascular resistance (+120%) among all treatment groups (P < 0.05). A simultaneous increase in endogenous adrenaline and noradrenaline concentrations could only be observed in the xenon/remifentanil group, whereas angiotensin II and vasopressin concentrations increased in all groups. In conclusion, xenon/remifentanil anaesthesia maintains MAP but reduces heart rate and CO and is associated with a considerable stimulation of vasopressor hormones in Beagle dogs. Therefore, xenon/remifentanil exerts a new quality of adverse haemodynamic effects different from volatile anaesthetics and may not perform better during studies of cardiovascular physiology.

Pulmonary vasodilation by acetazolamide during hypoxia: impact of methyl-group substitutions and administration route in conscious, spontaneously breathing dogs.

Acetazolamide (ACZ) prevents hypoxic pulmonary vasoconstriction (HPV) in isolated lungs, animals, and humans, but not by carbonic anhydrase (CA) inhibition. We studied administration routes in, and certain structural aspects of, ACZ critical to HPV inhibition. Analogs of ACZ during acute hypoxia were tested in unanesthetized dogs. Dogs breathed normoxic gas for 1 h (inspired O2 fraction = 0.21), followed by 10% O2 for 2 h (hypoxia) in these protocols: 1) controls; 2) ACZ intravenously (2 mg · kg(-1) · h(-1)); 3) ACZ orally (5 mg/kg, 12 and 1 h before the experiment); 4) inhaled ACZ (750 mg); 5) methazolamide (MTZ) intravenously (3 mg · kg(-1) · h(-1)); and 6) N-methyl-acetazolamide (NMA) intravenously (10 mg · kg(-1) · h(-1)). In controls, mean pulmonary arterial pressure (MPAP) increased 7 mmHg, and pulmonary vascular resistance (PVR) 224 dyn · s · cm(-5) with hypoxia (P < 0.05). With intravenous and inhaled ACZ, MPAP and PVR did not change during hypoxia. With oral ACZ, HPV was only slightly suppressed; MPAP increased 5 mmHg and PVR by 178 dyn · s · cm(-5) during hypoxia. With MTZ and NMA, the MPAP rise (4 ± 2 mmHg) was reduced, and PVR did not increase during hypoxia compared with normoxia (MTZ intravenous: 81 ± 77 and 68 ± 82 dyn · s · cm(-5) with NMA intravenous). Inhaled ACZ prevents HPV, but not without causing systemic CA inhibition. NMA, a compound lacking CA inhibiting effects by methylation at the sulfonamide moiety, and MTZ, a CA-inhibiting analog methylated at the thiadiazole ring, are only slightly less effective than ACZ in reducing HPV.

Detection of catecholamines and metanephrines by radio-immunoassay in canine plasma

This study investigated the applicability of two human radio-immunoassays (RIA) to detect epinephrine (EPI), norepinephrine (NE), and their O-methylated metabolites metanephrine (MN) and normetanephrine (NMN) in canine plasma. The analysis yielded a positive correlation between metabolites and their respective parent compounds: EPI and MN (r=0.63), NE and NMN (r=0.47), as well as between parent compounds, EPI and NE (r=0.48), and between metabolites MN and NMN (r=0.71). Moreover, EPI (r=0.99) and NE (r=0.77) concentrations determined by RIA did correlate positively with high pressure liquid chromatography (HPLC). However, there was limited agreement between both methods. It was concluded that complete validation tests for accuracy, precision and agreement are needed before this RIA can be applied to quantify catecholamines, metanephrine, and normetanephrine in canine plasma. The assay may prove to be a potential alternative to HPLC or tandem mass spectrometry in the work-up of pheochromocytoma and the detection of overall sympathetic activity in dogs.

Influence of goal-directed therapy with balanced crystalloid–colloid or unbalanced crystalloid solution on base excess

Objective To investigate changes in standard base excess (SBE) when administering two different infusion regimens for elective hip replacement within a goal-directed haemodynamic algorithm. Methods This prospective, double-blind, randomized, controlled study enrolled patients scheduled for primary hip replacement surgery, who were randomized to receive either an unbalanced crystalloid (chloride: 155.5 mmol/l) or a 1 : 1 mixture of a balanced crystalloid and a balanced colloid (6% w/v hydroxyethyl starch 130/0.42; chloride: 98 and 112 mmol/l, respectively). Fluid management was goal-directed to optimize stroke volume using oesophageal Doppler. Results A total of 40 patients (19 female/21 male) participated in the study. After surgery, median (25–75% percentiles) SBE was significantly lower in the unbalanced group compared with the balanced group: −2.0 mmol/l (−3.1 to −1.1) versus −0.4 mmol/l (−1.2 to 0.7), respectively. This difference was mainly due to greater plasma chloride concentrations in the unbalanced group. The amount of study medication required to reach haemodynamic stability (median 1200 ml) did not differ between the two groups. Conclusion SBE decreased in the unbalanced group without influence on fluid requirements and haemodynamic stability.