Meta-analysis of epidural analgesia in patients undergoing pancreatoduodenectomy.

Background: The optimal analgesic technique after pancreatoduodenectomy remains under debate. This study aimed to see whether epidural analgesia (EA) has superior clinical outcomes compared with non-epidural alternatives (N-EA) in patients undergoing pancreatoduodenectomy. Methods: A systematic review with meta-analysis was performed according to PRISMA guidelines. On 28 August 2018, relevant literature databases were searched. Primary outcomes were pain scores. Secondary outcomes were treatment failure of initial analgesia, complications, duration of hospital stay and mortality. Results: Three RCTs and eight cohort studies (25 089 patients) were included. N-EA treatments studied were: intravenous morphine, continuous wound infiltration, bilateral paravertebral thoracic catheters and intrathecal morphine. Patients receiving EA had a marginally lower pain score on days 0-3 after surgery than those receiving intravenous morphine (mean difference (MD) -0·50, 95 per cent c.i. -0·80 to -0·21; P < 0·001) and similar pain scores to patients who had continuous wound infiltration. Treatment failure occurred in 28·5 per cent of patients receiving EA, mainly for haemodynamic instability or inadequate pain control. EA was associated with fewer complications (odds ratio (OR) 0·69, 95 per cent c.i. 0·06 to 0·79; P < 0·001), shorter duration of hospital stay (MD -2·69 (95 per cent c.i. -2·76 to -2·62) days; P < 0·001) and lower mortality (OR 0·69, 0·51 to 0 93; P = 0·02) compared with intravenous morphine. Conclusion: EA provides marginally lower pain scores in the first postoperative days than intravenous morphine, and appears to be associated with fewer complications, shorter duration of hospital stay and less mortality.

Antecedentes: La técnica analgésica óptima tras una duodenopancreatectomía permanece en debate. El objetivo de este estudio fue analizar si la analgesia epidural (epidural analgesia, EA) presenta resultados clínicos superiores en comparación con las alternativas no epidurales (non­epidural alternatives, N­EA) en pacientes que se someten a una duodenopancreatectomía. Métodos: Se realizó una revisión sistemática con metaanálisis de acuerdo con las recomendaciones PRISMA. El 28 de agosto de 2018, se realizó una búsqueda en las bases de datos relevantes de la literatura. El objetivo primario fueron las puntuaciones de dolor. Los objetivos secundarios fueron el fracaso del tratamiento de la analgesia inicial, las complicaciones, la duración de la estancia hospitalaria y la mortalidad. Resultados: Se incluyeron tres ensayos aleatorizados y controlados y ocho estudios de cohortes (25.089 pacientes). Las N­EA estudiadas fueron: morfina intravenosa (iv), infiltración continua de la herida, catéteres torácicos paravertebrales bilaterales y morfina intratecal. Los pacientes con EA tuvieron una puntuación de dolor marginalmente más baja en los días postoperatorios 0 a 3 en comparación con la morfina iv (diferencia de medias (MD) = ­ 0,50, i.c. del 95% ­0,80 a ­0,21; P < 0,001) y puntuaciones de dolor similares en comparación con la infiltración continua de la herida. El fallo del tratamiento ocurrió en el 28,5% de los pacientes con EA, principalmente por inestabilidad hemodinámica o control inadecuado del dolor. La EA se asoció con menos complicaciones (razón de oportunidades, odds ratio, OR = 0,69, i.c. del 95% 0,061 a 0,79; P < 0,001), menor duración de la estancia hospitalaria (MD = ­2,69 días, i.c. del 95% ­2,76 a ­2,62; P < 0,001) y menor mortalidad en comparación con la morfina iv (OR = 0,69, i.c. del 95% 0,51 a 0,93; P = 0,01). Conclusión: La EA proporciona puntuaciones de dolor ligeramente más bajas en los primeros días postoperatorios en comparación con la morfina iv y parece asociarse con menos complicaciones, menor duración de la estancia hospitalaria y menor mortalidad.

A novel approach to identify responder subgroups and predictors of response to low- and high-dose capsaicin patches in postherpetic neuralgia.

BACKGROUND: Treatment of chronic pain conditions is commonly assessed at specific endpoints at preset times during or after treatment by analysis of the total study population. An alternative approach is the identification of specific patient subgroups characterized by differential response patterns in their analgesic response and to determine the presence of significant predictors of effect. METHODS: Data from four double-blind, randomized controlled trials on the efficacy of topical capsaicin 8% (Qutenza) versus an active control (capsaicin 0.04%) in patients with postherpetic neuropathic pain were combined. Longitudinal pharmacodynamic, mixture and covariate analyses were performed on the pooled dataset. RESULTS: Data from 1248 patients treated with Qutenza (n = 722) or topical low-dose capsaicin 0.04% (n = 526) were successfully analysed. Five distinct response subgroups were detected with different treatment efficacies, including a group of non-responders, a group showing partial analgesic effect and a group showing full analgesic effect. Active control and Qutenza had similar response profiles, but the proportional distribution of patients among the five response groups was in favour of Qutenza, with 40% less non-responders and 25% more patients showing a full analgesic response. For Qutenza, important predictors of efficacy were efficacy of lidocaine pretreatment and greater pretreatment pain score variability. CONCLUSIONS: The analyses indicate the existence of different response groups to treatment with Qutenza and an active control patch that may possibly be related to different pain mechanisms among these groups, despite a presumed common underlying disease process, and that require different treatment approaches among subgroups.

Perioperative infusions in paediatric patients: rationale for using Ringer-lactate solution with low dextrose concentration.

To assess the usefulness of Ringer-lactate solution with 0.9% dextrose, fluid therapy during surgery in paediatric patients was reviewed. From the literature, the need for intravenous (i.v.) infusion and water could be established. The need for sodium was also evident and use of normonatraemic i.v. solutions should be recommended to avoid hyponatraemia. Little data were found about the value of the other electrolytes. Dextrose requirements have been the subject of debate for the last two decades. The choice of dextrose concentration is a compromise between avoiding hypoglycaemia and hyperglycaemia. Four clinical trials assessing the use of Ringer-lactate solution with 0.9 or 1% dextrose in paediatric patients suggest that it is appropriate for routine infusion in paediatric patients during the perioperative period. However, fluid therapy during surgery has rarely been studied, probably because it is inexpensive, rarely leads to problems and is used in very different clinical settings. Development of consensus clinical guidelines on the use of electrolyte infusions in paediatric surgery would be helpful.

Does subanesthetic isoflurane affect the ventilatory response to acute isocapnic hypoxia in healthy volunteers?

BACKGROUND: Differences in results studying the effects of subanesthetic concentrations of volatile agents on the hypoxic ventilatory response may be related to the conditions under which the subjects were tested. In this study we investigated the effects of 0.1 minimum alveolar concentration (MAC) of isoflurane on the hypoxic ventilatory response without and with audiovisual stimulation. METHODS: Step decreases in arterial hemoglobin oxygen saturation from normoxia into hypoxia (arterial hemoglobin oxygen saturation 80% +/- 2%; duration of hypoxia 5 min) were performed in ten healthy subjects. We obtained four responses per subject: one without isoflurane in a darkened, quiet room; one without isoflurane with audiovisual input (music videos); one in a darkened room at 0.1 MAC isoflurane; and one at 0.1 MAC isoflurane with audiovisual input (subjects were addressed to keep their eyes open). Experiments were performed against a background of isocapnia (end-tidal carbon dioxide tension 1-1.4 mmHg above initial resting values). RESULTS: The hypoxic responses averaged 0.54 +/- 0.09 1.min-1.%-1 (without isoflurane in a darkened, quiet room), 0.27 +/- 0.06 l-min-1.%-1 (in a darkened room at 0.1 MAC isoflurane; P < 0.01), 0.56 +/- 0.131.min-1.%-1 (without isoflurane with audiovisual input), and 0.47 +/- 0.13 l.min-1.%-1 (at 0.1 MAC isoflurane with audiovisual input). Values are means +/- SE. During 0.1 MAC isoflurane administration, all subjects showed a depressed hypoxic response when not stimulated, while with stimulation two subjects had an increased response, four a decreased response and four an unchanged response compared to control. CONCLUSIONS: We observed an important effect of the study conditions on the effects that 0.1 MAC isoflurane has on the hypoxic ventilatory response. A depressant effect of subanesthetic isoflurane was found only when external stimuli to the subjects were absent. With extraneous audiovisual stimuli the effect of isoflurane on the response to hypoxia was more variable. On the average, however, the response then was not depressed by isoflurane.