Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

BACKGROUND: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. METHODS: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. RESULTS: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04–1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15–1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7–3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64–7.71) and mortality (RR=19.80; 95% CI, 5.87–66.7). CONCLUSIONS: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants

Arzneimittelinteraktionen von Phenylbutazon und Phenprocoumon bei einem Warmblutpferd

Ein 15-jähriger Oldenburger Wallach wurde zur Therapie einer Hufrehe während 3 Wochen einmal täglich oral mit 27 mg des Gerinnungshemmers Phenprocoumon bei gleichzeitiger Gabe von 2-4 g Phenylbutazon per os zweimal täglich. Nach dieser Behandlung wurde das Tier mit Kolikvorbericht und hochgradiger Schocksymptomatik an die Pferdeklinik der Universität Zürich überwiesen. Mittels der klinischen Untersuchung und der Laborwerte wurde eine erhöhte Blutungsneigung aufgrund von Arneimittelinteraktionen diagnostiziert. Die Behandlung des Pferdes erfolgte mit Vitamin-K1 (0.5 mg/kg, subkutan). Da sich der Allgemeinzustand des Tieres jedoch weiter verschlechterte, wurde das Pferd euthanasiert. Die Sektion des Tieres ergab hochgradige multifokale Hämorrhagien der Serosen und der inneren Organe sowie Blutungen in die Körperhöhlen. Dieser Fall zeigt, dass die gleichzeitige Gabe des Coumarinderivats Phenprocoumon mit Phenylbutazon Arzneimittelinteraktionen hervorrufen kann, die den antikoagulierenden Effekt des Coumarinderivats verstärken. Eine solche Kombinationstherapie ist aufgrund der erhöhten Blutungsgefahr kontraindiziert. Eine sinnvolle Behandlung des Pferdes mit Gerinnungshemmern bedarf daher einer strengen Indikation mit regelmässiger Kontrolle des Gerinnungsstatus unter Beachtung von potentiellen Interaktionen. Schlüsselwörter: Pferd, Gerinnungshemmer, Phenprocoumon, Phenylbutazon, Arzneimittelinteraktionen A 15 year old Oldenburger gelding was treated during 3 weeks for laminitis with the anticoagulant phenprocoumone (27 mg orally, once daily) and concurrent administration of phenylbutazone (2-4 g orally, twice daily). After this treatment the animal was presented to the Equine Clinic University of Zurich with a history of acute colic and advanced symptoms of shock. On the basis of the clinical signs and laboratory values, a diagnosis of combined drug induced coagulopathy was made. The horse was treated with the antidote Vitamine- K1 (0.5 mg/kg, subcutaneously). Eventually, the general condition of the animal worsened and it was therefore euthanized. Necropsy revealed profound, multifocal hemorrhagic diathesis of the serosal surface of the viscera, as well as bleeding into the visceral cavities. This case shows that concurrent administration of phenprocoumone and phenylbutazone may lead to drug interactions that increase the anticoagulation effect of the coumarine-derivative. Simultaneous use of coumarine-derivatives and phenylbutazone is therefore contraindicated due to the higher risk of bleeding. A reasonable treatment of horses with anticoagulants requires regular monitoring with constant evaluation of coagulation status and special attention to potential drug interactions. Keywords: Horse, anticoagulants, phenprocoumon, phenylbutazone, drug interaction