Effect of PEEP and I:E ratio on cerebral oxygenation in ARDS: an experimental study in anesthetized rabbit.

BACKGROUND: Although PEEP and inversed I:E ratio have been shown to improve gas exchange in ARDS, both can adversely affect systemic hemodynamics and cerebral perfusion. The goal of this study was to assess how changes in PEEP and I:E ratio affect systemic and cerebral oxygenation and perfusion in normal and injured lung. METHODS: Eight anesthetized Chinchilla-Bastard rabbits were ventilated at baseline with pressure-regulated volume control mode, VT = 6 ml/kg, PEEP = 6 cmH2O, FIO2 = 0.4; respiratory rate set for ETCO2 = 5.5%, and I:E = 1:2, 1:1 or 2:1 in random order. Ultrasonic carotid artery flow (CF), arterial (PaO2), jugular venous blood gases and near infrared spectroscopic cerebral oxygenation (∆HBO2) were recorded for each experimental condition. After induced lung injury, the animals were ventilated with PEEP = 9 followed by 6 cmH2O. RESULTS: At baseline, inverse-ratio ventilation (IRV) significantly reduced cerebral oxygenation (∆O2HB; - 27 at 1:2; - 15 at 1:1 vs. 0.27 µmol/L at 2:1; p < 0.05), due to a significant reduction in mean arterial pressure and CF without modifying gas exchange. In injured lung, IRV improved gas exchange but decreased cerebral perfusion without affecting brain oxygenation. The higher PEEP level, however, improved PaO2 (67.5 ± 19.3 vs. 42.2 ± 8.4, p < 0.05), resulting in an improved ∆HBO2 (- 13.8 ± 14.7 vs. -43.5 ± 21.3, p < 0.05), despite a drop in CF. CONCLUSIONS: Our data suggest that unlike moderate PEEP, IRV is not effective in improving brain oxygenation in ARDS. In normal lung, IRV had a deleterious effect on brain oxygenation, which is relevant in anesthetized patients.

Postoperative Analgesia after Laparoscopic Ovarian Cyst Resection: Double-blind Multicenter Randomized Control Trial Comparing Intraperitoneal Nebulization and Peritoneal Instillation of Ropivacaine.

STUDY OBJECTIVE: To compare the effects of local anesthetic intraperitoneal nebulization with intraperitoneal instillation during laparoscopic ovarian cystectomy on postoperative morphine consumption and pain. DESIGN: Multicenter, randomized, case-control trial. DESIGN CLASSIFICATION: Canadian Task Force Classification I. SETTING: University hospitals in Italy. PATIENTS: One hundred forty patients scheduled for laparoscopic ovarian cystectomy. INTERVENTIONS: Patients were randomized to receive either nebulization of ropivacaine 150 mg before surgery or instillation of ropivacaine 150 mg before surgery. Nebulization was performed using the Aeroneb Pro device (Aerogen, Galway, Ireland). MEASUREMENTS AND MAIN RESULTS: One hundred forty patients were enrolled, and 123 completed the study. There was no difference between the 2 groups in average morphine consumption (7.3 ± 7.5 mg in the nebulization group vs 9.2 ± 7.2 mg in the instillation group; p = .17). Eighty-two percent of patients in the nebulization group required morphine compared with 96% in the instillation group (p < .05). Patients receiving nebulization had a lower dynamic Numeric Ranking Scale compared with those in the instillation group in the postanesthesia care unit postanesthesia care unit and 4 hours after surgery (p < .05). Ten patients (15%) in the nebulization group experienced shivering in the postanesthesia care unit compared with 2 patients (4%) in the instillation group (p = .035). CONCLUSION: Nebulization of ropivacaine prevents the use of morphine in a significant proportion of patients, reduced postoperative pain during the first hours after surgery, and was associated with a higher incidence of postoperative shivering when compared with instillation.

Emergence delirium, pain or both? A challenge for clinicians.

BACKGROUND: Children commonly display early postoperative negative behavior (e-PONB) after general anesthesia, which includes emergence delirium (ED), discomfort, temperament, and pain. However, it is often difficult for the caregiver to discriminate between various aspects of e-PONB. OBJECTIVE: This prospective observational study evaluates the possibility to distinguish between ED and pain in young children using validated pediatric observational scales in the early postoperative phase. METHODS: Following institutional approval and written consent, children undergoing elective adenoidectomy and/or tonsillectomy were enrolled. Following standardized anesthesia, two trained observers simultaneously evaluated children's behavior with the Paediatric Anaesthesia Emergence Delirium Scale (PAED) and with the Face, Legs, Activity, Cry, Consolability scale (FLACC) at extubation, and at 5, 10, and 15 min. RESULTS: Of 150 children that completed the study, 32 (21%) had ED, 7 (5%) had pain, and 98 (65%) had simultaneously both ED and pain. The association of 'No eye contact', 'No purposeful action' and 'No awareness of surroundings' (ED1) had a sensitivity of 0.96 and a specificity of 0.80 (PPV 0.97, NPV 0.78) to identify ED. 'Inconsolability' and 'Restlessness' (ED2) had a sensitivity of 0.69 and a specificity of 0.88 (PPV 0.83 and NPV 0.78) to identify pain. CONCLUSION: It is difficult to differentiate between ED and pain using FLACC and PAED scores. 'No eye contact', 'No purposeful action', and 'No awareness of surroundings' significantly correlated with ED. 'Inconsolability' and 'Restlessness' are not reliable enough to identify pain or ED in the first 15 min after awakening.

Effects of peritoneal ropivacaine nebulization for pain control after laparoscopic gynecologic surgery.

STUDY OBJECTIVE: To evaluate the effects of peritoneal cold nebulization of ropivacaine on pain control after gynecologic laparoscopy. DESIGN: Evidence obtained from a properly designed, randomized, double-blind, placebo-controlled trial (Canadian Task Force classification I). SETTING: Tertiary care center. PATIENTS: One hundred thirty-five women with American Society of Anesthesiologists disease classified as ASA I-III who were scheduled to undergo operative laparoscopy. INTERVENTION: Patients were randomized to receive either nebulization of 30 mg ropivacaine before surgery (preoperative group), nebulization of 30 mg ropivacaine after surgery (postoperative group), instillation of 100 mg ropivacaine before surgery (instillation group), or instillation of saline solution (control group). Nebulization was performed using the Aeroneb Pro device. MEASUREMENT AND MAIN RESULTS: Pain scores, morphine consumption, and ambulation time were collected in the post-anesthesia care unit and at 4, 6, and 24 hours postoperatively. One hundred eighteen patients completed the study. Patients in the preoperative group reported lower pain Numeric Ranking Scale values compared with those in the control group (net difference 2 points; 95% confidence interval [CI], 0.3-3.1 at 4 hours, 1-3 at 6 hours, and 0.7-3 at 24 hours; p = .01) Patients in the preoperative group consumed significantly less morphine than did those in the control group (net difference 7 mg; 95% CI, 0.7-13; p = .02). More patients who received nebulization walked without assistance within 12 hours after awakening than did those in the instillation and control groups (net difference 15%; 95% CI, 6%-24%; p = .001). CONCLUSIONS: Cold nebulization of ropivacaine before surgery reduced postoperative pain and morphine consumption and was associated with earlier walking without assistance.

Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial.

BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.

Rapid reorganization of the Milan metropolitan public safety answering point operations during the initial phase of the COVID-19 outbreak in Italy.

Objective: To quantify how the first public announcement of confirmed coronavirus disease 2019 (COVID-19) in Italy affected a metropolitan region's emergency medical services (EMS) call volume and how rapid introduction of alternative procedures at the public safety answering point (PSAP) managed system resources. Methods: PSAP processes were modified over several days including (1) referral of non-ill callers to public health information call centers; (2) algorithms for detection, isolation, or hospitalization of suspected COVID-19 patients; and (3) specialized medical teams sent to the PSAP for triage and case management, including ambulance dispatches or alternative dispositions. Call volumes, ambulance dispatches, and response intervals for the 2 weeks after announcement were compared to 2017-2019 data and the week before. Results: For 2 weeks following outbreak announcement, the primary-level PSAP (police/fire/EMS) averaged 56% more daily calls compared to prior years and recorded 9281 (106% increase) on Day 4, averaging ∼400/hour. The secondary-level (EMS) PSAP recorded an analogous 63% increase with 3863 calls (∼161/hour; 264% increase) on Day 3. The COVID-19 response team processed the more complex cases (n = 5361), averaging 432 ± 110 daily (∼one-fifth of EMS calls). Although community COVID-19 cases increased exponentially, ambulance response intervals and dispatches (averaging 1120 ± 46 daily) were successfully contained, particularly compared with the week before (1174 ± 40; P = 0.02). Conclusion: With sudden escalating EMS call volumes, rapid reorganization of dispatch operations using tailored algorithms and specially assigned personnel can protect EMS system resources by optimizing patient dispositions, controlling ambulance allocations and mitigating hospital impact. Prudent population-based disaster planning should strongly consider pre-establishing similar highly coordinated medical taskforce contingencies.

Pressure support ventilation + sigh in acute hypoxemic respiratory failure patients: study protocol for a pilot randomized controlled trial, the PROTECTION trial.

BACKGROUND: Adding cyclic short sustained inflations (sigh) to assisted ventilation yields optimizes lung recruitment, decreases heterogeneity and reduces inspiratory effort in patients with acute hypoxemic respiratory failure (AHRF). These findings suggest that adding sigh to pressure support ventilation (PSV) might decrease the risk of lung injury, shorten weaning and improve clinical outcomes. Thus, we conceived a pilot trial to test the feasibility of adding sigh to PSV (the PROTECTION study). METHODS: PROTECTION is an international randomized controlled trial that will be conducted in 23 intensive care units (ICUs). Patients with AHRF who have been intubated from 24 h to 7 days and undergoing PSV from 4 to 24 h will be enrolled. All patients will first undergo a 30-min sigh test by adding sigh to clinical PSV for 30 min to identify early oxygenation responders. Then, patients will be randomized to PSV or PSV + sigh until extubation, ICU discharge, death or day 28. Sigh will be delivered as a 3-s pressure control breath delivered once per minute at 30 cmH2O. Standardized protocols will guide ventilation settings, switch back to controlled ventilation, use of rescue treatments, performance of spontaneous breathing trial, extubation and reintubation. The primary endpoint of the study will be to verify the feasibility of PSV + sigh evaluated through reduction of failure to remain on assisted ventilation during the first 28 days in the PSV + sigh group versus standard PSV (15 vs. 22%). Failure will be defined by switch back to controlled ventilation for more than 24 h or use of rescue treatments or reintubation within 48 h from elective extubation. Setting the power to 80% and first-risk order to 5%, the computed size of the trial is 129 patients per arm. DISCUSSION: PROTECTION is a pilot randomized controlled trial testing the feasibility of adding sigh to PSV. If positive, it will provide physicians with an effective addition to standard PSV for lung protection, able to reduce failure of assisted ventilation. PROTECTION will provide the basis for a future larger trial aimed at verifying the impact of PSV + sigh on 28-day survival and ventilator-free days. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03201263 . Registered on 28 June 2017.

Hemophagocytic lymphohistiocytosis complicated by multiorgan failure: A case report.

RATIONALE: We present a case of hemophagocytic lymphohistiocytosis (HLH) with severe pulmonary complication and acute respiratory distress syndrome (ARDS) hospitalized in our intensive care unit (ICU) in 2014; distinctive trait of this case has been the challenging diagnosis, with a bone marrow biopsy always negative, the severe pulmonary complication with ARDS and severe pulmonary hypertension, and the ferritin temporal kinetics that precisely followed the clinical course of disease. PATIENT CONCERNS: A 32-year-old woman from the Philippines first diagnosed with upper airway infection, was subsequently hospitalized in infectious disease department and treated for community acquired pneumonia. DIAGNOSES: After clinical picture worsened with a profound respiratory insufficiency, the patient was intubated and transferred to our ICU. During this hospitalization, the clinical picture of fever, cutaneous rashes, lymphadenitis, hepatitis, leukopenia, anemia, hyperferritinemia, hypertriglyceridemia, high level of auto-antibodies, and low NK activity suggested an hemophagocytic lymphohistiocytosis syndrome, even if bone marrow biopsy was negative for hemophagocytosis. INTERVENTIONS: Immunosuppressive therapy with dexamethasone and etoposide was started, and the patient was discharged from ICU 4 months after admission. LESSONS: HLH is a rare disorder of the mononuclear phagocytic system, characterized by systemic proliferation of non- neoplastic histiocytes. The diagnosis is often challenging and not all of the diagnostic criteria may be present at the same time; this case shows how complex the diagnosis could be, how hematic ferritin levels could help in following the course of the disease, and the possibility of severe pulmonary complication either due to the disease itself and to possible sovra infections.

Peritoneal Nebulization of Ropivacaine during Laparoscopic Cholecystectomy: Dose Finding and Pharmacokinetic Study.

Background. Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption after laparoscopic surgery. The aim of this multicenter double-blind randomized controlled trial was to assess the efficacy of different doses and dose-related absorption of ropivacaine when nebulized in the peritoneal cavity during laparoscopic cholecystectomy. Methods. Patients were randomized to receive 50, 100, or 150 mg of ropivacaine 1% by peritoneal nebulization through a nebulizer. Morphine consumption, pain intensity in the abdomen, wound and shoulder, time to unassisted ambulation, discharge time, and adverse effects were collected during the first 48 hours after surgery. The pharmacokinetics of ropivacaine was evaluated using high performance liquid chromatography. Results. Nebulization of 50 mg of ropivacaine had the same effect of 100 or 150 mg in terms of postoperative morphine consumption, shoulder pain, postoperative nausea and vomiting, activity resumption, and hospital discharge timing (>0.05). Plasma concentrations did not reach toxic levels in any patient, and no significant differences were observed between groups (P > 0.05). Conclusions. There is no enhancement in analgesic efficacy with higher doses of nebulized ropivacaine during laparoscopic cholecystectomy. When administered with a microvibration-based aerosol humidification system, the pharmacokinetics of ropivacaine is constant and maintains an adequate safety profile for each dosage tested.

Human Genetic Variability Contributes to Postoperative Morphine Consumption.

UNLABELLED: High interindividual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain, and single nucleotide polymorphisms (SNPs) within opioid receptor µ 1 (OPRM1), catechol-O-methyltransferase (COMT), uridine diphosphate glucose-glucuronosyltransferase-2B7, and estrogen receptor (ESR1) gene loci to elucidate genetic prediction of opioid consumption. We analyzed 20 SNPs in 201 unrelated Caucasian patients who underwent abdominal surgery and who were receiving postoperative patient-controlled analgesia-administered morphine. Morphine consumption and pain intensity were dependent variables; age and sex were covariates. A haplotype of 7 SNPs in OPRM1 showed significant additive effects on opioid consumption (P = .007); a linear regression model including age and 9 SNPs in ESR1, OPRM1, and COMT explained the highest proportion of variance of morphine consumption (10.7%; P = .001). The minimal model including 3 SNPs in ESR1, OPRM1, and COMT explained 5% of variance (P = .007). We found a significant interaction between rs4680 in COMT and rs4986936 in ESR1 (P = .007) on opioid consumption. SNPs rs677830 and rs540825 of OPRM1 and rs9340799 of ESR1 were nominally associated with pain Numeric Rating Scale scores. Combinations of genetic variants within OPRM1, COMT, and ESR1 better explain variability in morphine consumption than single genetic variants. Our results contribute to the development of genetic markers and statistical models for future diagnostic tools for opioid consumption/efficacy. PERSPECTIVE: This article presents the efforts dedicated to detect correlations between the genetic polymorphisms and the clinical morphine effect self-administered by patients using a patient-controlled analgesia pump after major surgery. The clinical effect is expressed in terms of morphine consumption and pain scores. REGISTERED ON CLINICALTRIALS.GOV: NCT01233752.