Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

INTRODUCTION: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. MATERIAL AND METHODS: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. RESULTS: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. CONCLUSIONS: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

Prognostic impact of ventilation-perfusion defects and pulmonary diffusing capacity after single lung transplantation.

BACKGROUND: Ventilation-perfusion (VQ) scintigraphy and lung function testing are often used to assess allograft function after single lung transplantation (SLTX). However, it is unknown whether allograft defects on VQ scintigraphy presage all-cause mortality after SLTX. OBJECTIVE: To investigate whether allograft defects on VQ scintigraphy portend poorer lung function and increased mortality after SLTX. METHODS: We retrospectively identified 45 consecutive patients in which a VQ scintigraphy was performed as part of the routine workup 12 weeks after SLTX. VQ scintigraphies were scored for matched and mismatched perfusion defects in the allograft. Lung function testing was performed according to established guidelines six months after SLTX. Time to all-cause mortality was the endpoint. RESULTS: 19 (42%) patients had matched VQ defects. After a median follow-up of 4.1 (IQR 1.5-7.9) years since SLTX, 35 (78%) had died. Those with matched defects in the allograft had lower diffusing capacity (mean 42 [SD 14] versus mean 54 [SD 18] % of predicted, p < .05) and increased mortality (univariable HR 2.06, 95% CI: 1.05-4.06, p = .04). However, in multivariate analysis, only lower post-transplantation diffusing capacity remained associated with mortality (HR 1.08, 95% CI: 1.02-1.30 per % lower diffusing capacity of predicted, p = .003). CONCLUSION: In SLTX patients, a lower diffusing capacity appeared to explain the increased mortality among those with matched VQ defects in the allograft.

Pulmonary thromboembolism as a complication of lung transplantation.

Post-transplantation mortality after lung transplantation (LTX) is higher than for other solid organ transplantations. Thoracic surgery is associated with increased risk of thromboembolic complications, and as LTX recipients lack the collateral bronchial circulation, pulmonary thromboembolism (PTE) may represent a pertinent yet largely underdiagnosed cause of post-transplantation respiratory failure. In this systematic review, we sought to elucidate the occurrence and predilection site of PTE after LTX, and its potential impact on LTX-associated mortality. Based on twelve original articles identified by a systematic search strategy in PubMed, we found that PTE was reported in 4% of LTX recipients, and 38% of these events occurred within the first 30 days after the LTX procedure. In single-lung transplantation (SLTX) recipients, 12% were diagnosed with PTE, with 92% of these affecting the allograft. Of LTX patients diagnosed with PTE, 11% died within 1 year after LTX and 75% of these deaths occurred within the first 30 days. Our findings suggest that PTE is a potentially underdiagnosed cause of early post-LTX respiratory failure. This should be confirmed in larger studies with systematic follow-up diagnostic imaging.