Opioids and immunosupression in oncological postoperative patients.

INTRODUCTION: Recent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on Post-Anesthesia Care Unit (PACU)-acquired infection after a schedule of sedoanalgesia of at least 6 days. METHOD: All patients over 18 years of age with a unit admission of more than 4 days were consecutively selected. The study population was the one affected by surgical pathology of any origin where sedation was based on any hypnotic and the opioid remifentanil was used as analgesic for at least 96 hours in continuous perfusion. Patients who died during admission to the unit and those with combined analgesia (peripheral or neuroaxial blocks) were excluded. Bivariate analysis was performed to determine risk factors for infection acquired in the unit. A comparative study between periods of 6 days before and after the cessation of remifentanil was performed. Paired samples test and McNemar test was used for quantitative and categorical variables, respectively. RESULTS: There were 1,789 patients admitted to the PACU during the study and the population eligible was constituted for 102 patients. The incidence rate of PACU-acquired infection was 38 per 1,000 PACU days. Ventilator-associated pneumonia was the most frequently diagnosed PACU-acquired infection. Pseudomona aeruginosa was the most frequently isolated microorganism. Hospital mortality was 36.27%. No statistically significant differences were seen in the incidence of HAI in cancer patients in relation to discontinuation of remifentanil (p=0.068). CONCLUSION: The baseline state of immunosuppression of cancer patients does not imply a higher incidence of HAI in relation to the interruption of remifentanil. It would be of interest to carry out a multicenter PACU study that included immunological patterns.

Opioids and immunosupression in oncological postoperative patients / Opioides e imunossupressão em pacientes oncológicos pós-cirúrgicos

Summary Introduction: Recent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on Post-Anesthesia Care Unit (PACU)-acquired infection after a schedule of sedoanalgesia of at least 6 days. Method: All patients over 18 years of age with a unit admission of more than 4 days were consecutively selected. The study population was the one affected by surgical pathology of any origin where sedation was based on any hypnotic and the opioid remifentanil was used as analgesic for at least 96 hours in continuous perfusion. Patients who died during admission to the unit and those with combined analgesia (peripheral or neuroaxial blocks) were excluded. Bivariate analysis was performed to determine risk factors for infection acquired in the unit. A comparative study between periods of 6 days before and after the cessation of remifentanil was performed. Paired samples test and McNemar test was used for quantitative and categorical variables, respectively. Results: There were 1,789 patients admitted to the PACU during the study and the population eligible was constituted for 102 patients. The incidence rate of PACU-acquired infection was 38 per 1,000 PACU days. Ventilator-associated pneumonia was the most frequently diagnosed PACU-acquired infection. Pseudomona aeruginosa was the most frequently isolated microorganism. Hospital mortality was 36.27%. No statistically significant differences were seen in the incidence of HAI in cancer patients in relation to discontinuation of remifentanil (p=0.068). Conclusion: The baseline state of immunosuppression of cancer patients does not imply a higher incidence of HAI in relation to the interruption of remifentanil. It would be of interest to carry out a multicenter PACU study that included immunological patterns.

Resumo Introdução: Recentes pesquisas utilizando animais demonstraram efeitos imunossupressores depois da suspensão de opiáceos, associados a um maior risco de infecção nosocomial. O objetivo desta investigação foi determinar o impacto da interrupção do opioide remifentanilo em uma Unidade de Reanimação Pós-cirúrgica (URP) nas infecções associadas aos cuidados da saúde depois de uma pauta de sedoanalgesia de ao menos 6 dias. Método: Foram relacionados de forma consecutiva todos os pacientes maiores de 18 anos com internação na unidade superior a 4 dias. A população investigada foi aquela afetada por patologia cirúrgica de qualquer origem, na qual a sedação esteve baseada em qualquer hipnótico e como analgésico, foi utilizado o opioide remifentanilo durante pelo menos 96 horas em perfusão contínua. Foram excluídos os pacientes que faleceram durante a internação na unidade e aqueles com analgesia combinada (bloqueios periféricos ou neuroaxiais). Foi realizada uma análise bivariante para determinar fatores de risco para a infecção adquirida na unidade. Foi realizada uma investigação comparativa entre períodos dos 6 dias anteriores e posteriores à interrupção de remifentanilo. Utilizamos o teste de amostras pareadas e a prova de McNemar para as variáveis quantitativas e categóricas, respectivamente. Resultados: O número de pacientes internados na URP durante o período de investigação foi de 1.789. Depois de aplicar os critérios de inclusão e exclusão, a população elegível ficou constituída por 102 pacientes. A densidade de incidência de infecção de forma global foi de 38 por cada 1.000 dias de internamento. A pneumonia associada à ventilação mecânica foi a infecção adquirida mais frequente e Pseudomona aeruginosa, o micro-organismo mais frequentemente isolado. A mortalidade hospitalar foi de 36,27%. Não foram observadas diferenças estatisticamente significativas na incidência de IACS em pacientes oncológicos em relação à descontinuação de remifentanilo (p=0,068). Conclusão: O estado basal de imunossupressão dos pacientes oncológicos não implica uma maior incidência de IACS em relação à interrupção do remifentanilo. Seria interessante a realização de uma investigação multicêntrica de URP que incluísse padrões imunológicos.

Bioavailability of generic 0.05% difluprednate emulsion in the aqueous humor, cornea, and conjunctiva of New Zealand rabbits after a single dose compared with commercial difluprednate.

BACKGROUND: To determine the concentration after a single dose of generic 0.05% difluprednate and commercial difluprednate in the aqueous humor, cornea, and conjunctiva of New Zealand rabbits, a preclinical study in 72 male New Zealand white rabbits was performed. A single dose (50 µL) of two 0.05% difluprednate ophthalmic formulations was instilled in both eyes. Conjunctiva, cornea, and aqueous humor samples were collected at nine time points over 8 h (four animals per time point). The active metabolite of difluprednate, 17-difluoroprednisolone-butyrate (DFB), concentrations was quantified using HPLC. RESULTS: Measurable levels of DFB were quantified in all three ocular tissues. After a single instillation, the highest concentration of difluprednate was found between 30 and 60 min in the conjunctiva, cornea, and aqueous humor, respectively. There was no significant difference between both formulations in any tissue at any time point. After 3 h, no metabolites of either emulsion were found in any tissue. CONCLUSIONS: Difluprednate penetrates into different ocular tissues. Generic difluprednate has a similar pharmacokinetic profile compared with commercial difluprednate.

Histopathological changes on the ocular surface of New Zealand white rabbits after instillation of a fixed combination of 0.09 % xanthan gum and 0.1 % chondroitin sulfate.

The aim of this study was to evaluate the histopathological changes in a model of New Zealand white rabbits after the ocular instillation of a fixed combination containing 0.09 % xanthan gum and 0.1 % chondroitin sulfate for 15 days. This was a preclinical study which compared the previously described combination with placebo on an animal model of sixteen New Zealand white rabbits. The intervention consisted of the instillation of one drop of a fixed combination containing 0.09 % xanthan gum and 0.1 % chondroitin sulfate on the right eye of each rabbit 6 times per day (every 2 h) in a 12-hour period for 15 days. The left eyes were used as control. Assessments on the anterior and posterior segment, ocular signs, and specific ocular surface characteristics were conducted at days 0, 1, 2, 4, 7, 10, and 15. Histopathological studies of the corneal and conjunctival epithelium were performed at the end of the intervention. No significant changes were observed during the assessments of the anterior and posterior segments. No differences in the number of goblet cells between groups were reported. The histopathological study of the corneal basement membrane's thickness, stromal, and conjunctival epithelium did not show significant changes between groups. The use of a fixed-dose combination containing 0.09 % xanthan gum and 0.1 % chondroitin sulfate on the ocular surface of New Zealand white rabbits every 2 h for 15 days causes no histopathological changes in anterior/posterior segments, nor a decrease in the number of goblet cells compared with placebo.