In high-risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA.

Background and ObjectivesManagement of postoperative pain after laparoscopic segmental colonic resections remains controversial. We compared 2 methods of analgesia within an Enhanced Recovery After Surgery (ERAS) program. The goal of the study was to investigate whether administration of intrathecal bupivacaine/morphine would lead to an enhanced recovery.MethodsA single-center, randomized, double-blind controlled trial was performed (NL43488.101.13). Patients scheduled for laparoscopic segmental intestinal resections were considered. Exclusion criteria were patients in whom contraindications to spinal anesthesia were present, conversion to open surgery, and gastric and rectal surgery. The intervention group received single-shot intrathecal bupivacaine/morphine (12.5 mg/300 μg), with an altered dose for older patients. The control group received a sham procedure and a bolus of piritramide (0.1 mg/kg). Both groups received standardized general anesthesia and a patient-controlled intravenous analgesia pump as postoperative analgesia. All patients were treated according to an ERAS protocol. A decrease in days to “fit for discharge” was the primary outcome.ResultsFifty-six patients were enrolled. Intervention group patients were fit for discharge earlier (median of 3 vs 4 days, P = 0.044). Furthermore, there was a significant decrease in opioid use and lower pain scores on the first postoperative day in the intervention group. There were no differences in adverse events (except for more pruritus), time to mobilization, fluid administration, or patient satisfaction.ConclusionsThis randomized controlled trial shows that intrathecal morphine is a more effective method of postoperative analgesia in laparoscopic surgery than intravenous opioids within an ERAS program. Recovery is faster and less painful with intrathecal morphine. Other studies have confirmed these results, although data on faster recovery are new and require confirmation in future trials.Clinical Trial RegistrationThis study was registered at ClinicalTrials.gov, identifier NCT02284282.

Summary Robot‐assisted radical prostatectomy causes discomfort in the immediate postoperative period. This randomised controlled trial investigated if intrathecal bupivacaine/morphine, in addition to general anaesthesia, could be beneficial for the postoperative quality of recovery. One hundred and fifty‐five patients were randomly allocated to an intervention group that received intrathecal 12.5 mg bupivacaine/300 μg morphine (20% dose reduction in patients > 75 years) or a control group receiving a subcutaneous sham injection and an intravenous loading dose of 0.1 mg.kg−1 morphine. Both groups received standardised general anaesthesia and the same postoperative analgesic regimen. The primary outcome was a decrease in the Quality of Recovery‐15 (QoR‐15) questionnaire score on postoperative day 1. The intervention group (n = 76) had less reduction in QoR‐15 on postoperative day 1; median (IQR [range]) 10% (1–8 [−60% to 50%]) vs. 13% (5–24 [−6% to 50%]), p = 0.019, and used less morphine during the admission; 2 mg (1–7 [0–41 mg]) vs. 15 mg (12–20 [8–61 mg]), p < 0.001. Furthermore, they perceived lower pain scores during exertion; numeric rating scale (NRS) 3 (1–6 [0–9]) vs. 5 (3–7 [0–9]), p = 0.001; less bladder spasms (NRS 1 (0–2 [0–10]) vs. 2 (0–5 [0–10]), p = 0.001 and less sedation; NRS 2 (0–3 [0–10]) vs. 3 (2–6 [0–10]), p = 0.005. Moreover, the intervention group used less rescue medication. Pruritus was more severe in the intervention group; NRS 4 (1–7 [0–10]) vs. 0 (0–1 [0–10]), p = 0.000. We conclude that despite a modest increase in the incidence of pruritus, multimodal pain management with intrathecal bupivacaine/morphine remains a viable option for robot‐assisted radical prostatectomy.

In this review, published data regarding inhaled AMB are summarized, including available descriptions regarding preparation, dose, efficacy, and toxicity, and its place in therapy is discussed. The results from the studies that were reviewed in this article indicate that inhaled AMB may have a place in the prophylactic regimens of patients with prolonged neutropenia and in lung transplant recipients. Furthermore, nebulized (liposomal) AMB may have a place in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in patients with corticosteroid-dependent ABPA.

The nebulization of amphotericin B desoxycholate (AMB-DOC), liposomal amphotericin B (L-AMB), amphotericin B lipid complex (ABLC) and amphotericin B colloidal dispersion (ABCD) has been investigated. Particle sizes of generated aerosol droplets were measured. Pulmonary amphotericin B deposition and amphotericin B concentration in blood directly after nebulization and at six weeks after nebulization was measured in healthy rats. The efficacy of nebulized amphotericin B formulations was evaluated in persistently granulocytopenic rats with invasive pulmonary aspergillosis. Treatment was given either after or before fungal inoculation. The endpoint was survival of animals. Aerosol particle sizes, expressed as the values for the mass median diameter were 1.38, 2.43, 0.90 and 2.29 microm for AMB-DOC, L-AMB, ABLC and ABCD, respectively. Amphotericin B concentrations in the lungs directly after nebulization exceeded the minimum inhibitory concentration of Aspergillus fumigatus and amphotericin B was still detected in lungs of rats at six weeks after nebulization. Treatment, started at 16 h after fungal inoculation, resulted in a significantly prolonged survival as compared with sham-treated rats for all four formulations. Prophylactic treatment at one week before fungal inoculation resulted in a significantly prolonged survival for all four formulations. Aerosol treatment given at two weeks before inoculation was effective only for AMB-DOC and L-AMB, whereas treatment given at six weeks resulted in a significantly prolonged survival for L-AMB only. All commercially available amphotericin B preparations could be nebulized efficiently and may be of value in the prophylactic treatment of invasive pulmonary aspergillosis.