Risks of serious adverse events with non-steroidal anti-inflammatory drugs in gastrointestinal surgery: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly recommended for perioperative opioid-sparing multimodal analgesic treatments. Concerns regarding the potential for serious adverse events (SAEs) associated with perioperative NSAID treatment are especially relevant following gastrointestinal surgery. We assessed the risks of SAEs with perioperative NSAID treatment in patients undergoing gastrointestinal surgery. METHODS: We conducted a systematic review of randomised clinical trials assessing the harmful effects of NSAIDs versus placebo, usual care or no intervention in patients undergoing gastrointestinal surgery. The primary outcome was an incidence of SAEs. We systematically searched for eligible trials in five major databases up to January 2024. We performed risk of bias assessments to account for systematic errors, trial sequential analysis (TSA) to account for the risks of random errors, performed meta-analyses using R and used the Grading of Recommendations Assessment, Development and Evaluation framework to describe the certainty of evidence. RESULTS: We included 22 trials enrolling 1622 patients for our primary analyses. Most trials were at high risk of bias. Meta-analyses (risk ratio 0.78; 95% confidence interval [CI] 0.51-1.19; I2 = 4%; p = .24; very low certainty of evidence) and TSA indicated a lack of information on the effects of NSAIDs compared to placebo on the risks of SAEs. Post-hoc beta-binomial regression sensitivity analyses including trials with zero events showed a reduction in SAEs with NSAIDs versus placebo (odds ratio 0.73; CI 0.54-0.99; p = .042). CONCLUSION: In adult patients undergoing gastrointestinal surgery, there was insufficient information to draw firm conclusions on the effects of NSAIDs on SAEs. The certainty of the evidence was very low.

Dopamine plasma clearance is increased in piglets compared to neonates during continuous dopamine infusion.

AIM: Piglets models have often been used to study the effects of dopamine infusion on hypotension in neonates. However, piglets need higher doses of dopamine than neonates to increase blood pressure. We investigated whether this difference was due to interspecific difference in dopamine pharmacokinetics. METHODS: Arterial blood samples were drawn from six neonates admitted to the neonatal intensive care unit of Copenhagen University Hospital and 20 newborn piglets during continuous dopamine infusion. Furthermore, to estimate the piglet plasma dopamine half-life, blood samples were drawn at 2.5-minute intervals after the dopamine infusion was discontinued. The plasma dopamine content was analysed by high-performance liquid chromatography with electrochemical detection. RESULTS: The dopamine displayed first-order kinetics in piglets and had a half-life of 2.5 minutes, while the median plasma clearance was 627.9 mL/kg/minute (interquartile range 452.6-1914.4). Both piglets and neonates showed large interindividual variations in plasma clearance, but the median tended to be lower in neonates (384.9, interquartile range 114.2-480.2 mL/kg/minute). CONCLUSION: Our results suggest that pharmacokinetic differences may explain the interspecific difference in required doses of dopamine infusion to increase blood pressure. This is important when translating the results obtained in piglet models to treating neonatal hypotension with dopamine.

Dopamine therapy is associated with impaired cerebral autoregulation in preterm infants.

AIM: Hypotension is a common problem in newborn infants and is associated with increased mortality and morbidity. Dopamine is the most commonly used antihypotensive drug therapy, but has never been shown to improve neurological outcomes. This study tested our hypothesis that dopamine affects cerebral autoregulation (CA). METHODS: Near-infrared spectroscopy was used to measure the cerebral oxygenation index in 60 very preterm infants, and mean arterial blood pressure was monitored towards the end of their first day of life. Measurements were performed continuously for two to three hour periods. CA was quantified as the cerebral oximetry index (COx). RESULTS: We treated 13 of the 60 infants (22%) with dopamine during the measurements. COx was higher in the dopamine group than the untreated group (0.41 ± 0.25 vs. 0.08 ± 0.25, p < 0.001). Blood pressure tended to be lower in the dopamine group, but the anticipated difference in cerebral oxygenation was not detected. The need for mechanical ventilation in the first day of life and incidences of mortality was higher in the dopamine group. CONCLUSION: Dopamine therapy was associated with decreased CA in preterm infants. We were unable to determine whether dopamine directly impaired CA or was merely an indicator of illness.

Deviating vital signs in continuous monitoring prior to discharge and risk of readmission: an observational study.

Premature discharge may result in readmission while longer hospitalization may increase risk of complications such as immobilization and reduce hospital capacity. Continuous monitoring detects more deviating vital signs than intermittent measurements and may help identify patients at risk of deterioration after discharge. We aimed to investigate the association between deviating vital signs detected by continuous monitoring prior to discharge and risk of readmission within 30 days. Patients undergoing elective major abdominal surgery or admitted with acute exacerbation of chronic obstructive pulmonary disease were included in this study. Eligible patients had vital signs monitored continuously within the last 24 h prior to discharge. The association between sustained deviated vital signs and readmission risk was analyzed by using Mann-Whitney's U test and Chi-square test. A total of 51 out of 265 patients (19%) were readmitted within 30 days. Deviated respiratory vital signs occurred frequently in both groups: desaturation < 88% for at least ten minutes was seen in 66% of patients who were readmitted and in 62% of those who were not (p = 0.62) while desaturation < 85% for at least five minutes was seen in 58% of readmitted and 52% of non-readmitted patients (p = 0.5). At least one sustained deviated vital sign was detected in 90% and 85% of readmitted patients and non-readmitted patients, respectively (p = 0.2). Deviating vital signs prior to hospital discharge were frequent but not associated with increased risk of readmission within 30 days. Further exploration of deviating vital signs using continuous monitoring is needed.

Mechanical and vasomotor properties of piglet isolated middle cerebral artery.

Piglets are often used as experimental models for studying cerebrovascular responses in newborn infants. However, the mechanical characteristics of piglets' middle cerebral arteries (MCA) are not well characterized. Additionally, the vessels' response to dopamine, the most commonly used vasopressor in newborns, is not characterized in piglets' MCA. Finally, the influence of preterm birth on the dopamine response is not known. The aim of this current was to compare by wire myography the active and passive mechanical characteristics and dopamine concentration-response relations of MCAs isolated from preterm and term newborn piglets. Second-order branches of the MCA with a diameter <400 µm were chosen for study. The active and passive mechanical properties were comparable between vessels from six preterm (90% gestation, nsegments = 11) and nine term (nsegments = 22) newborn piglets. The response to increasing concentrations of dopamine was biphasic, starting with vasodilation in the 1 nmol/L-0.3 µmol/L concentration range followed by vasoconstriction at higher concentrations. The response was very similar between the two groups. In conclusion, the mechanical properties of the MCA as well as the response to dopamine were comparable between term and 90% gestation preterm piglets.

Quantifying cerebral hypoxia by near-infrared spectroscopy tissue oximetry: the role of arterial-to-venous blood volume ratio.

Tissue oxygenation estimated by near-infrared spectroscopy (NIRS) is a volume-weighted mean of the arterial and venous hemoglobin oxygenation. In vivo validation assumes a fixed arterial-to-venous volume-ratio (AV-ratio). Regulatory cerebro-vascular mechanisms may change the AV-ratio. We used hypotension to investigate the influence of blood volume distribution on cerebral NIRS in a newborn piglet model. Hypotension was induced gradually by inflating a balloon-catheter in the inferior vena cava and the regional tissue oxygenation from NIRS ( rStO 2 , NIRS ) was then compared to a reference ( rStO 2 , COX ) calculated from superior sagittal sinus and aortic blood sample co-oximetry with a fixed AV-ratio. Apparent changes in the AV-ratio and cerebral blood volume (CBV) were also calculated. The mean arterial blood pressure (MABP) range was 14 to 82 mmHg. PaCO 2 and SaO 2 were stable during measurements. rStO 2 , NIRS mirrored only 25% (95% Cl: 21% to 28%, p < 0.001 ) of changes in rStO 2 , COX . Calculated AV-ratio increased with decreasing MABP (slope: ? 0.007 · mmHg ? 1

Cerebral autoregulation in the preterm newborn using near-infrared spectroscopy: a comparison of time-domain and frequency-domain analyses.

The aim was to compare two conventional methods used to describe cerebral autoregulation (CA): frequency-domain analysis and time-domain analysis. We measured cerebral oxygenation (as a surrogate for cerebral blood flow) and mean arterial blood pressure (MAP) in 60 preterm infants. In the frequency domain, outcome variables were coherence and gain, whereas the cerebral oximetry index (COx) and the regression coefficient were the outcome variables in the time domain. Correlation between coherence and COx was poor. The disagreement between the two methods was due to the MAP and cerebral oxygenation signals being in counterphase in three cases. High gain and high coherence may arise spuriously when cerebral oxygenation decreases as MAP increases; hence, time-domain analysis appears to be a more robust­and simpler­method to describe CA.