Sérgio Martins Pereira

Purpose: Pain may pose significant challenges in the intensive care unit, especially in mechanically ventilated patients. Methadone has recently emerged as an alternative option for eliciting acute analgesia. In this systematic review, we evaluated the use of methadone in mechanically ventilated patients in the intensive care unit. Source: We searched MEDLINE, EMBASE, Wiley’s Cochrane […] ABSTRACT Purpose: Pain may pose significant challenges in the intensive care unit, especially in mechanically ventilated patients. Methadone has recently emerged as an alternative option for eliciting acute analgesia. In this systematic review, we evaluated the use of methadone in mechanically ventilated patients in the intensive care unit. Source: We searched MEDLINE, EMBASE, Wiley’s Cochrane […]

BACKGROUND AND OBJECTIVES: Acute pain following laparoscopic cholecystectomy is most intense in the first 24 h. The use of shorter-acting opioids for pain management may contribute to increased postoperative morbidity. The combination of methadone and ketamine has been associated with lower postoperative pain scores and less opioid use. We aimed to determine whether the combination of ketamine and methadone improves the quality of recovery. METHODS: This prospective cohort study included patients undergoing laparoscopic cholecystectomy. Patients who received either methadone alone or a combination of methadone and ketamine (0.3 mg/kg) were followed up for 24 h after surgery. The primary outcome was the quality of recovery, measured using the quality of recovery-40 (QoR-40) questionnaire. Secondary outcomes included postoperative pain intensity, opioid consumption, and the incidence of nausea and vomiting. RESULTS: The QoR-40 scores were higher in patients who received methadone and ketamine than in those who received methadone alone [197 (194.7–198) versus 195 (189–197), P = 0.01]. Postoperative pain scores, the incidence of postoperative nausea and vomiting, and postoperative opioid use were similar between the groups. The combination of methadone and ketamine was not associated with lower incidence of moderate-to-severe pain in propensity score analysis. CONCLUSIONS: Although the combination of methadone and ketamine showed a slight increase in QoR40 scores at 24 h postoperatively, the observed difference between the groups was not clinically significant. Moreover, the absence of a reduction in postoperative pain intensity and similar perioperative opioid consumption between the groups further support the hypothesis that small, isolated doses of ketamine may not be effective in improving recovery quality compared with methadone alone.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9–60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose–response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

Rationale: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious. Objectives: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP). Methods: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS. Measurements and Main Results: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients). Conclusions: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.