RESUMEN
The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly-d,l-Lactic Acid (PDLLA) and/or Polycaprolactone (PCL-1 or PCL-2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97-100 days after implantation. Following the administration of a 30 µg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre-dose respiratory rate (RR). The BIOPIN NTX-implanted dogs were exposed to escalating doses of intravenous fentanyl (30 µg/kg, 60 µg/kg, 90 µg/kg, and 120 µg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 µg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 µg/kg and especially at 120 µg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.
Asunto(s)
Implantes Absorbibles , Fentanilo , Naltrexona , Antagonistas de Narcóticos , Insuficiencia Respiratoria , Perros , Animales , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Masculino , Naltrexona/administración & dosificación , Naltrexona/farmacología , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/prevención & control , Proyectos Piloto , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/farmacología , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Preparaciones de Acción RetardadaRESUMEN
BACKGROUND: Nasal cannulas and face masks are common oxygenation tools used in conventional oxygen therapy for patients undergoing endoscopic surgery with sedation. However, as a novel supraglottic ventilation technique, the application of supraglottic jet oxygenation and ventilation (SJOV) in endoscopic surgery has not been well established. METHOD: We searched six electronic databases from inception to January 16, 2024, to assess the oxygenation/ventilation efficacy and side effects of the of SJOV in endoscopic surgery. The primary outcome was the incidence of hypoxemia. The secondary outcomes were the incidence of respiratory depression and adverse effects (nasal bleeding, sore throat, and dry mouth). RESULTS: Nine trials involving 2017 patients were included. The results demonstrated that the incidence of hypoxemia was lower in the SJOV group compared with the conventional oxygen therapy (COT) group [9 trails; 2017 patients; risk ratio (RR) = 0.18; 95% confidence interval (CI), (0.11-0.28)]. Subgroup analyses showed that SJOV reduced the incidence of hypoxemia in the high-risk group but had no effect on the low-risk group. The incidence of respiratory depression is lower in SJOV than in COT, but has increased side effects such as dry mouth. There was no statistically significant difference in nose bleeding or sore throat between the two groups. CONCLUSION: Compared with the COT, the SJOV decreased the incidence of hypoxemia in high-risk patients during endoscopic surgery with sedation. There was an increased risk of dry mouth, but not of nose bleeding or sore throat, during endoscopic surgery under sedation.
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Endoscopía , Ventilación con Chorro de Alta Frecuencia , Hipoxia , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Hipoxia/prevención & control , Hipoxia/etiología , Hipoxia/epidemiología , Endoscopía/efectos adversos , Endoscopía/métodos , Ventilación con Chorro de Alta Frecuencia/métodos , Ventilación con Chorro de Alta Frecuencia/efectos adversos , Sedación Consciente/efectos adversos , Sedación Consciente/métodos , Incidencia , Insuficiencia Respiratoria/prevención & control , Insuficiencia Respiratoria/etiología , Terapia por Inhalación de Oxígeno/métodos , Resultado del TratamientoRESUMEN
La atrofia muscular espinal (AME) 5q es una de las enfermedades neuromusculares de mayor incidencia en la infancia. Sin embargo, la prevalencia de AME tipo 1, su forma más severa de presentación, es menor debido a muertes prematuras evitables antes de los dos años por insuficiencia ventilatoria subtratada. La irrupción de nuevos tratamientos modificadores de la enfermedad pueden cambiar dramáticamente este pronóstico y es una oportunidad para actualizar el manejo respiratorio, a través de cuidados estandarizados básicos, preferentemente no invasivos, abordando la debilidad de los músculos respiratorios, la insuficiencia tusígena y ventilatoria, con un enfoque preventivo. La siguiente revisión literaria entrega estrategias para evitar la intubación y la traqueostomía usando soporte ventilatorio no invasivo (SVN), reclutamiento de volumen pulmonar (RVP) y facilitación de la tos. Se analizan en detalle los protocolos de extubación en niños con AME tipo 1.
Spinal muscular atrophy (SMA) 5q is one of the neuromuscular diseases with the highest incidence in childhood. Nevertheless, the prevalence of its most severe form SMA1 is lower due to premature preventable deaths before two years of age related to ventilatory insufficiency undertreated. The emergence of new disease-modifying treatments can dramatically change this prognosis and is an opportunity to update respiratory management, through basic standardized care, mostly non-invasive, addressing respiratory muscles pump weakness, cough and ventilatory insufficiency with a preventive approach. This literature review provides consensus recommendations for strategies to avoid intubation and tracheostomy using noninvasive ventilatory support (NVS), lung volume recruitment (LVR), and cough facilitation. Extubation protocols in children with SMA type 1 are analyzed in detail.
Asunto(s)
Humanos , Niño , Atrofia Muscular Espinal/terapia , Insuficiencia Respiratoria/prevención & control , Unidades de Cuidado Intensivo Pediátrico , Desconexión del Ventilador , Tos , Extubación Traqueal , Ventilación no Invasiva , Mediciones del Volumen PulmonarRESUMEN
BACKGROUND: Postoperative complications, particularly respiratory complications, are of significant clinical concern in patients undergoing elective thoracic surgery. Dexamethasone (DXM), commonly administered to prevent postoperative nausea and vomiting (PONV), has potential anti-inflammatory effects that might be beneficial in reducing these complications. We aimed to investigate whether intraoperative DXM administration could mitigate the occurrence of respiratory complications following elective thoracic surgery. METHODS: We conducted a single-center observational study, including patients who underwent elective thoracic surgery from 2012 to 2020. The primary outcome was the onset of acute respiratory failure within 7 days post-surgery. Secondary outcomes encompassed other postoperative complications, duration of hospital stay, and mortality within 30 days post-surgery. An overlap propensity score analysis was employed to estimate the treatment effect. RESULTS: We included 1,247 adult patients, 897 who received dexamethasone (DXM) and 350 who served as controls. Intraoperative dexamethasone administration was associated with a significant reduction in respiratory complications with an adjusted relative risk (RR) of 0.65 (95% CI: 0.43-0.97). There was also a significant decline in composite infectious criteria with an adjusted RR of 0.76 (95% CI: 0.63-0.93). Cardiac complications were also assessed as a composite criterion, and a significant reduction was observed (adjusted RR, 0.68; 95% CI, 0.51-0.9). However, there were no association with mechanical complications, mortality within 30 days (adjusted RR of 0.43, 95% CI: 0.17-1.09) or in the length of hospital stay (adjusted RR of 0.85, 95% CI: 0.71-1.02). CONCLUSIONS: Dexamethasone administration was associated with a reduction in postoperative respiratory complications. Further prospective studies are needed to confirm these findings.
Asunto(s)
Dexametasona , Cuidados Intraoperatorios , Complicaciones Posoperatorias , Insuficiencia Respiratoria , Procedimientos Quirúrgicos Torácicos , Humanos , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Procedimientos Quirúrgicos Torácicos/efectos adversos , Anciano , Insuficiencia Respiratoria/prevención & control , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Estudios de Cohortes , Cuidados Intraoperatorios/métodos , Tiempo de Internación/estadística & datos numéricos , Adulto , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéuticoRESUMEN
OBJECTIVE: The current standards of postoperative respiratory monitoring on medical-surgical floors involve spot-pulse oximetry checks every 4-8 h, which can miss the opportunity to detect prolonged hypoxia and acute hypercapnia. Continuous respiratory monitoring can recognize acute respiratory depression episodes; however, the existing evidence is limited. We sought to review the current evidence on the effectiveness of continuous pulse oximetry (CPOX) with and without capnography versus routine monitoring and their effectiveness for detecting postoperative respiratory failure, opioid-induced respiratory depression, and preventing downstream adverse events. METHODS: We performed a systematic literature search on Ovid Medline, Embase, and Cochrane Library databases for articles published between 1990 and April 2023. The study protocol was registered in Prospero (ID: 439467), and PRISMA guidelines were followed. The NIH quality assessment tool was used to assess the quality of the studies. Pooled analysis was conducted using the software R version 4.1.1 and the package meta. The stability of the results was assessed using sensitivity analysis. DESIGN: Systematic Review and Meta-Analysis. SETTING: Postoperative recovery area. PATIENTS: 56,538 patients, ASA class II to IV, non-invasive respiratory monitoring, and post-operative respiratory depression. INTERVENTIONS: Continuous pulse oximetry with or without capnography versus routine monitoring. MEASUREMENTS: Respiratory rate, oxygen saturation, adverse events, and rescue events. RESULTS: 23 studies (17 examined CPOX without capnography and 5 examined CPOX with capnography) were included in this systematic review. CPOX was better at recognizing desaturation (SpO2 < 90%) OR: 11.94 (95% CI: 6.85, 20.82; p < 0.01) compared to standard monitoring. No significant differences were reported for ICU transfer, reintubation, and non-invasive ventilation between the two groups. CONCLUSIONS: Oxygen desaturation was the only outcome better detected with CPOX in postoperative patients in hospital wards. These comparisons were limited by the small number of studies that could be pooled for each outcome and the heterogeneity between the studies.
Asunto(s)
Analgésicos Opioides , Insuficiencia Respiratoria , Humanos , Analgésicos Opioides/efectos adversos , Frecuencia Respiratoria , Capnografía/métodos , Monitoreo Fisiológico/métodos , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/prevención & control , Insuficiencia Respiratoria/diagnóstico , Oximetría/métodos , Complicaciones Posoperatorias/diagnóstico , HospitalesRESUMEN
BACKGROUND: Dexmedetomidine sedation has advantages, such as low incidence of respiratory depression and prolonged block duration, but also significant disadvantages, such as slow onset, high rate of sedation failure, and a long context-sensitive half-life. Remimazolam provides rapid sedation and recovery, high sedation efficacy and has minimal hemodynamic effects. We hypothesized that patients who received remimazolam would require less rescue midazolam than dexmedetomidine. METHODS: Patients (n=103) scheduled for surgery under spinal anesthesia were randomized to receive dexmedetomidine (DEX group) or remimazolam (RMZ group) targeting a Modified Observer's Assessment of Alertness/Sedation score of 3 or 4. Rescue midazolam was administered if the patient failed to be sedated after the initial loading dose or despite infusion rate adjustment. RESULTS: Rescue midazolam administration was significantly higher in the DEX group (0% vs 39.2%; p<0.001). Patients in the RMZ group reached the target sedation level more rapidly. The incidences of bradycardia (0% vs 25.5%; p<0.001) and hypertension (0% vs 21.6%; p<0.001) were higher in the DEX group. Respiratory depression occurred at a higher rate in the RMZ group (21.2% vs 2.0%; p=0.002), but no patients required manual ventilation. Patients in the RMZ group recovered faster, had a shorter PACU stay and higher satisfaction scores. Hypotensive episodes in the PACU were more frequent in the DEX group (1.9% vs 29.4%; p<0.001). CONCLUSIONS: Remimazolam showed excellent sedation efficacy, minimal hemodynamic effects, and fewer adverse events in the PACU than dexmedetomidine. However, it is important to note that respiratory depression was more frequent with the use of remimazolam. TRIAL REGISTRATION NUMBER: NCT05447507.
Asunto(s)
Anestesia Raquidea , Benzodiazepinas , Dexmedetomidina , Insuficiencia Respiratoria , Humanos , Midazolam/efectos adversos , Hipnóticos y Sedantes/efectos adversos , Dexmedetomidina/efectos adversos , Anestesia Raquidea/efectos adversos , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/prevención & control , Extremidad Inferior/cirugíaRESUMEN
STUDY OBJECTIVE: Obesity is associated with an increased risk of sleep-disordered breathing (SDB) and postoperative pulmonary complications (PPCs). Postoperative noninvasive respiratory support (NRS) has been recommended to obese patients despite the controversy about its benefit. The network meta-analysis (NMA) was used in this study to compare the effect of different methods of NRS on preventing PPCs in obese patients. DESIGN: This study is a network meta-analysis. SETTING: Post-anesthesia care unit and inpatient ward. PATIENTS: 20 randomized controlled trials involving 1184 obese patients were included in the final analysis. INTERVENTIONS: One of the four NRS techniques, which include continuous positive airway pressure (CPAP), bi-level positive airway pressure (BiPAP), high-flow nasal cannula (HFNC), or conventional oxygen therapy (COT), was performed after general anesthesia. MEASUREMENTS: The primary outcome was the incidence of PPCs, e.g., atelectasis, pneumonia, hypoxemia, and respiratory failure. The secondary outcomes included the incidence of oxygen treatment failure and anastomotic leakage, oxygenation index, and length of hospital stay (LOS). RevMan 5.3 and STATA 16.0 were used to analyze the results and any potential bias. MAIN RESULTS: Compared with COT, BiPAP and HFNC were both effective in reducing the occurrence of postoperative atelectasis. There were no significant differences in the occurrence of other PPCs including pneumonia, hypoxemia and respiratory failure between the four NRS techniques. CPAP and HFNC were superior to other techniques in improving oxygenation and shortening LOS respectively. No differences were found in oxygen treatment failure and anastomotic leakage between the patients with different NRS. HFNC ranked the first in five of the eight outcomes (hypoxemia, respiratory failure, treatment failure, anastomotic leakage, LOS) in this review by the surface under the cumulative ranking curve (SUCRA). CONCLUSION: Among the four postoperative NRS techniques, HFNC seems to be the optimal choice for obese patients which shows certain advantages in reducing the risk of PPCs and shortening LOS.
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Ventilación no Invasiva , Neumonía , Atelectasia Pulmonar , Insuficiencia Respiratoria , Humanos , Fuga Anastomótica/etiología , Fuga Anastomótica/terapia , Extubación Traqueal , Metaanálisis en Red , Terapia por Inhalación de Oxígeno/métodos , Oxígeno , Cánula , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/prevención & control , Obesidad/complicaciones , Hipoxia/etiología , Atelectasia Pulmonar/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Neumonía/etiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The pathophysiological characteristics of the respiratory system of obese patients differ from those of non-obese patients. Few studies have evaluated the effects of high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) on the prognosis of obese patients. We here compared the effects of these two techniques on the prevention of reintubation after extubation for obese patients. METHODS: Data were extracted from the Medical Information Mart for Intensive Care database. Patients who underwent HFNC or NIV treatment after extubation were assigned to the HFNC or NIV group, respectively. The reintubation risk within 96 hours postextubation was compared between the two groups using a doubly robust estimation method. Propensity score matching was performed for both groups. RESULTS: This study included 757 patients (HFNC group: n=282; NIV group: n=475). There was no significant difference in the risk of reintubation within 96 hours after extubation for the HFNC group compared with the NIV group (OR 1.50, p=0.127). Among patients with body mass index ≥40 kg/m2, the HFNC group had a significantly lower risk of reintubation within 96 hours after extubation (OR 0.06, p=0.016). No significant differences were found in reintubation rates within 48 hours (15.6% vs 11.0%, p=0.314) and 72 hours (16.9% vs 13.0%, p=0.424), as well as in hospital mortality (3.2% vs 5.2%, p=0.571) and intensive care unit (ICU) mortality (1.3% vs 5.2%, p=0.108) between the two groups. However, the HFNC group had significantly longer hospital stays (14 days vs 9 days, p=0.005) and ICU (7 days vs 5 days, p=0.001) stays. CONCLUSIONS: This study suggests that HFNC therapy is not inferior to NIV in preventing reintubation in obese patients and appears to be advantageous in severely obese patients. However, HFNC is associated with significantly longer hospital stays and ICU stays.
Asunto(s)
Ventilación no Invasiva , Insuficiencia Respiratoria , Humanos , Estudios Retrospectivos , Extubación Traqueal/efectos adversos , Cánula , Terapia por Inhalación de Oxígeno/métodos , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/prevención & control , Obesidad/complicaciones , Obesidad/terapiaRESUMEN
Opioids are effective analgesics, but they can have harmful adverse effects, such as addiction and potentially fatal respiratory depression. Naloxone is currently the only available treatment for reversing the negative effects of opioids, including respiratory depression. However, the effectiveness of naloxone, particularly after an opioid overdose, varies depending on the pharmacokinetics and the pharmacodynamics of the opioid that was overdosed. Long-acting opioids, and those with a high affinity at the µ-opioid receptor and/or slow receptor dissociation kinetics, are particularly resistant to the effects of naloxone. In this review, the authors examine the pharmacology of naloxone and its safety and limitations in reversing opioid-induced respiratory depression under different circumstances, including its ability to prevent cardiac arrest.
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Sobredosis de Droga , Paro Cardíaco , Sobredosis de Opiáceos , Insuficiencia Respiratoria , Humanos , Naloxona/farmacología , Naloxona/uso terapéutico , Analgésicos Opioides/efectos adversos , Antagonistas de Narcóticos/farmacología , Antagonistas de Narcóticos/uso terapéutico , Sobredosis de Opiáceos/tratamiento farmacológico , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/prevención & control , Insuficiencia Respiratoria/tratamiento farmacológico , Sobredosis de Droga/tratamiento farmacológico , Paro Cardíaco/inducido químicamente , Paro Cardíaco/tratamiento farmacológico , Paro Cardíaco/prevención & controlRESUMEN
PURPOSE: This study investigated the incidence of postoperative pulmonary complications (PPC) when high-flow nasal cannula therapy (HFNC) is used prophylactically after pediatric cardiac surgery, and evaluated its efficacy. METHODS: This was a single-arm prospective interventional study that was conducted in a tertiary teaching hospital with eight beds in the pediatric cardiac ICU after approval by the Ethics Committee. One-hundred children under the age of 48 months who were scheduled for cardiac surgery for congenital heart disease were recruited. HFNC was used for 24 h after extubation at a 2 L/kg/min flow rate. The primary outcome was the incidence of PPC within 48 h after extubation. PPC was defined as atelectasis and acute respiratory failure meeting certain criteria. We considered prophylactic HFNC as effective if the prevalence of PPC was < 10%, based on previous reports of reintubation rates of 6%-9% after pediatric cardiac surgery. RESULTS: A total of 91 patients were finally included in the analysis. The incidence of PPC within 48 h after extubation was 18.7%, whereas atelectasis was observed in 13.2%, and acute respiratory failure in 8.8%. Reintubation rate within 48 h after extubation was 0%. CONCLUSIONS: We found the incidence of PPC with prophylactic HFNC after planned extubation after pediatric cardiac surgery. However, the incidence was > 10%; therefore, we could not demonstrate its efficacy in this single-arm study. Further studies are needed to investigate whether the HFNC could be adapted as first-line oxygen therapy after pediatric cardiac surgery.
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Procedimientos Quirúrgicos Cardíacos , Atelectasia Pulmonar , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Niño , Preescolar , Humanos , Extubación Traqueal/efectos adversos , Cánula/efectos adversos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Terapia por Inhalación de Oxígeno , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Atelectasia Pulmonar/epidemiología , Atelectasia Pulmonar/etiología , Atelectasia Pulmonar/prevención & control , Síndrome de Dificultad Respiratoria/complicaciones , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/prevención & controlAsunto(s)
Ventilación no Invasiva , Insuficiencia Respiratoria , Humanos , Extubación Traqueal , Respiración Artificial , Insuficiencia del Tratamiento , Obesidad/complicaciones , Obesidad/terapia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/prevención & control , Desconexión del VentiladorRESUMEN
BACKGROUND: Pulmonary complications are an important cause of morbidity and mortality after surgery. We evaluated the clinical effectiveness of noninvasive ventilation (NIV) in preventing postoperative acute respiratory failure. METHODS: This is an open, multicentre randomised trial that included patients at high risk of postoperative pulmonary complications after elective or semi-urgent surgery with an Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score ≥45. Patients were randomly assigned to intermittent prophylactic face-mask NIV for 6-8 h day-1 or usual postoperative care. The primary outcome was in-hospital acute respiratory failure within 7 days after surgery. Patients who underwent surgery and postoperative extubation were included in the modified intended-to-treat analysis. Results are presented as n (%) and odds ratios (ORs) with 95% confidence intervals. RESULTS: Between November 2017 and October 2019, 266 patients were randomised and 253 included in the main analysis. Of these, 203 (80.2%) were male with a mean age of 68 (11) yr and an ARISCAT score of 53 (6); 237 subjects (93.7%) underwent cardiac or thoracic surgery. There were 125 patients allocated to prophylactic NIV and 128 to usual care. Unplanned treatment termination occurred in 58 subjects in the NIV group, which was linked to NIV discomfort for 36 subjects. There was no difference in the incidence of the primary outcome of postoperative acute respiratory failure between treatment groups (NIV: 30 of 125 subjects [24.0%] vs usual care: 35 of 128 subjects [27.3%]; OR 0.97 [0.90-1.04]; P=0.54). CONCLUSIONS: Prophylactic NIV was difficult to implement after high-risk surgery because of low patient compliance. Prophylactic NIV did not prevent acute respiratory failure. CLINICAL TRIAL REGISTRATION: NCT03629431 and EudraCT 2017-001011-36.
Asunto(s)
Ventilación no Invasiva , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Humanos , Masculino , Anciano , Femenino , Ventilación no Invasiva/métodos , Cuidados Posoperatorios , Pulmón , Resultado del Tratamiento , Síndrome de Dificultad Respiratoria/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/prevención & controlRESUMEN
OBJECTIVE: To assess the effect of preoperative prophylactic corticosteroid use on short-term outcomes after oncologic esophagectomy. BACKGROUND: Previous studies have shown that prophylactic corticosteroid use may decrease the risk of respiratory failure following esophagectomy by attenuating the perioperative systemic inflammation response. However, its effectiveness has been controversial, and its impact on mortality remains unknown. METHODS: Data of patients who underwent oncologic esophagectomy between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting, propensity score matching, and instrumental variable analyses were performed to investigate the associations between prophylactic corticosteroid use and short-term outcomes, such as in-hospital mortality and respiratory failure, adjusting for potential confounders. RESULTS: Among 35,501 eligible patients, prophylactic corticosteroids were used in 22,620 (63.7%) patients. In-hospital mortality, respiratory failure, and severe respiratory failure occurred in 924 (2.6%), 5440 (15.3%), and 2861 (8.1%) patients, respectively. In stabilized inverse probability of treatment weighting analyses, corticosteroids were significantly associated with decreased in-hospital mortality [odds ratio (OR)=0.80; 95% confidence interval (CI): 0.69-0.93], respiratory failure (OR=0.84; 95% CI: 0.79-0.90), and severe respiratory failure (OR=0.87; 95% CI: 0.80-0.95). Corticosteroids were also associated with decreased postoperative length of stay and total hospitalization costs. The proportion of anastomotic leakage did not differ with the use of Propensity score matching and instrumental variable analysis demonstrated similar results. CONCLUSIONS: Prophylactic corticosteroid use in oncologic esophagectomy was associated with lower in-hospital mortality as well as decreased respiratory failure and severe respiratory failure, suggesting a potential benefit for preoperative corticosteroid use in esophagectomy.
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Neoplasias Esofágicas , Insuficiencia Respiratoria , Humanos , Mortalidad Hospitalaria , Estudios Retrospectivos , Pacientes Internos , Esofagectomía/efectos adversos , Japón/epidemiología , Corticoesteroides/uso terapéutico , Neoplasias Esofágicas/cirugía , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/prevención & controlRESUMEN
Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation). Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease. Design, Setting, and Participants: Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021. Interventions: Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685). Main Outcomes and Measures: The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels. Results: Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups. Conclusions and Relevance: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery. Trial Registration: anzctr.org.au Identifier: ACTRN12617000821392.
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Puente Cardiopulmonar , Cardiopatías Congénitas , Óxido Nítrico , Respiración Artificial , Insuficiencia Respiratoria , Fármacos del Sistema Respiratorio , Australia , Gasto Cardíaco Bajo/etiología , Gasto Cardíaco Bajo/prevención & control , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Puente Cardiopulmonar/efectos adversos , Puente Cardiopulmonar/instrumentación , Puente Cardiopulmonar/métodos , Método Doble Ciego , Femenino , Cardiopatías Congénitas/cirugía , Humanos , Lactante , Recién Nacido , Masculino , Países Bajos , Nueva Zelanda , Óxido Nítrico/administración & dosificación , Óxido Nítrico/uso terapéutico , Oxigenadores , Recuperación de la Función , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/prevención & control , Insuficiencia Respiratoria/terapia , Fármacos del Sistema Respiratorio/administración & dosificación , Fármacos del Sistema Respiratorio/uso terapéutico , SíndromeRESUMEN
The decision of extubation is difficult in ICUs because in case of reintubation mortality is particularly high. High-flow nasal cannula oxygen therapy (HFNC) and noninvasive ventilation (NIV) are two respiratory supports that help to improve oxygenation, to decrease work of breathing and to decrease the risk of reintubation in selected patients. In the ICU, HFNC seems effective in patient with mild hypoxemia at time of extubation (risk of reintubation<10%) while prophylactic NIV is particularly effective in patients at high-risk of extubation failure (risk of reintubation>20%). Patients older than 65 years, those with underlying chronic cardiac or respiratory disease, or with hypercapnia are patients at high-risk easily identified at time of extubation. The best oxygenation strategy for management of post-extubation respiratory failure is unknown. HFNC has never been assessed in this setting, and NIV may have deleterious effects in patients with post-extubation respiratory failure. In postoperative patients, standard oxygen is sufficient even after major planned surgery (risk of intubation<5%), but should probably be switched to HFNC in patients with hypoxemia (risk of intubation 10-15%) and further to NIV in patients with respiratory failure with hypoxemia and clinical signs of respiratory distress (risk of intubation 50%).
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Ventilación no Invasiva , Insuficiencia Respiratoria , Extubación Traqueal/efectos adversos , Humanos , Hipoxia/complicaciones , Hipoxia/terapia , Oxígeno , Terapia por Inhalación de Oxígeno , Insuficiencia Respiratoria/prevención & control , Insuficiencia Respiratoria/terapiaRESUMEN
IntroductionEmergency abdominal surgery is associated with a high risk of postoperative complications. One of the most serious is postoperative respiratory failure (PRF), with reported rates up to 20%-30% and attributable 30-day mortality that can exceed 20%.Lung-protective ventilation, especially the use of low tidal volume, may help reducing the risk of lung injury. The role of positive end-expiratory pressure (PEEP) and recruitment manoeuvre (RM) remains however debated. We aim to evaluate whether a strategy aimed at increasing alveolar recruitment by using higher PEEP levels and RM could be more effective at reducing PRF and mortality after emergency abdominal surgery than a strategy aimed at minimising alveolar distension by using lower PEEP levels without RM. METHODS AND ANALYSIS: The IMPROVE-2 study is a multicentre randomised, parallel-group clinical trial of 680 patients requiring emergency abdominal surgery under general anaesthesia. Patients will be randomly allocated in a 1:1 ratio to receive either low PEEP levels (≤5 cm H2O) without RM or high PEEP levels individually adjusted according to driving pressure in addition to RM, stratified by centre and according to the presence of shock and hypoxaemia at randomisation. The primary endpoint is a composite of PRF and all-cause mortality by day 30 or hospital discharge. Data will be analysed on the intention-to-treat principle and a per-protocol basis. ETHICS AND DISSEMINATION: IMPROVE-2 trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in February 2021. Results will be submitted for publication in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03987789.
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Respiración Artificial , Insuficiencia Respiratoria , Abdomen/cirugía , Humanos , Estudios Multicéntricos como Asunto , Respiración con Presión Positiva/métodos , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/métodos , Insuficiencia Respiratoria/prevención & control , Volumen de Ventilación PulmonarRESUMEN
INTRODUCTION: Patients with obesity are considered to be at high risk of acute respiratory failure (ARF) after extubation in intensive care unit (ICU). Compared with oxygen therapy, non-invasive ventilation (NIV) may prevent ARF in high-risk patients. However, these strategies have never been compared following extubation of critically ill patients with obesity. Our hypothesis is that NIV is associated with less treatment failure compared with oxygen therapy in patients with obesity after extubation in ICU. METHODS AND ANALYSIS: The NIV versus oxygen therapy after extubation in patients with obesity in ICUs protocol (EXTUB-obese) trial is an investigator-initiated, multicentre, stratified, parallel-group unblinded trial with an electronic system-based randomisation. Patients with obesity defined as a body mass index ≥30 kg/m² will be randomly assigned in the 'NIV-group' to receive prophylactic NIV applied immediately after extubation combined with high-flow nasal oxygen (HFNO) or standard oxygen between NIV sessions versus in the 'oxygen therapy group' to receive oxygen therapy alone (HFNO or standard oxygen,). The primary outcome is treatment failure within the 72 hours, defined as reintubation for mechanical ventilation, switch to the other study treatment, or premature study-treatment discontinuation (at the request of the patient or for medical reasons such as gastric distention). The single, prespecified, secondary outcome is the incidence of ARF until day 7. Other outcomes analysed will include tracheal intubation rate at day 7 and day 28, length of ICU and hospital stay, ICU mortality, day 28 and day 90 mortality. ETHICS AND DISSEMINATION: The study project has been approved by the appropriate ethics committee 'Comité-de-Protection-des-Personnes Ile de FranceV-19.04.05.70025 Cat2 2019-A00956-51'. Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. If use of NIV shows positive effects, teams (medical and surgical) will use NIV following extubation of critically ill patients with obesity. TRIAL REGISTRATION NUMBER: NCT04014920.
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Ventilación no Invasiva , Insuficiencia Respiratoria , Extubación Traqueal/efectos adversos , Humanos , Unidades de Cuidados Intensivos , Estudios Multicéntricos como Asunto , Ventilación no Invasiva/métodos , Obesidad/complicaciones , Obesidad/terapia , Oxígeno , Respiración Artificial/efectos adversos , Insuficiencia Respiratoria/prevención & control , Insuficiencia Respiratoria/terapiaRESUMEN
OBJECTIVES: Lung- and diaphragm-protective ventilation is a novel concept that aims to limit the detrimental effects of mechanical ventilation on the diaphragm while remaining within limits of lung-protective ventilation. The premise is that low breathing effort under mechanical ventilation causes diaphragm atrophy, whereas excessive breathing effort induces diaphragm and lung injury. In a proof-of-concept study, we aimed to assess whether titration of inspiratory support based on diaphragm effort increases the time that patients have effort in a predefined "diaphragm-protective" range, without compromising lung-protective ventilation. DESIGN: Randomized clinical trial. SETTING: Mixed medical-surgical ICU in a tertiary academic hospital in the Netherlands. PATIENTS: Patients (n = 40) with respiratory failure ventilated in a partially-supported mode. INTERVENTIONS: In the intervention group, inspiratory support was titrated hourly to obtain transdiaphragmatic pressure swings in the predefined "diaphragm-protective" range (3-12 cm H2O). The control group received standard-of-care. MEASUREMENTS AND MAIN RESULTS: Transdiaphragmatic pressure, transpulmonary pressure, and tidal volume were monitored continuously for 24 hours in both groups. In the intervention group, more breaths were within "diaphragm-protective" range compared with the control group (median 81%; interquartile range [64-86%] vs 35% [16-60%], respectively; p < 0.001). Dynamic transpulmonary pressures (20.5 ± 7.1 vs 18.5 ± 7.0 cm H2O; p = 0.321) and tidal volumes (7.56 ± 1.47 vs 7.54 ± 1.22 mL/kg; p = 0.961) were not different in the intervention and control group, respectively. CONCLUSIONS: Titration of inspiratory support based on patient breathing effort greatly increased the time that patients had diaphragm effort in the predefined "diaphragm-protective" range without compromising tidal volumes and transpulmonary pressures. This study provides a strong rationale for further studies powered on patient-centered outcomes.
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Diafragma/metabolismo , Pulmón/metabolismo , Respiración Artificial/normas , Trabajo Respiratorio/fisiología , Diafragma/fisiopatología , Femenino , Humanos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Respiración Artificial/métodos , Respiración Artificial/estadística & datos numéricos , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/prevención & control , Insuficiencia Respiratoria/terapia , Trabajo Respiratorio/efectos de los fármacosRESUMEN
New psychoactive substance (NPS) opioids have proliferated within the international drug market. While synthetic opioids are traditionally composed of fentanyl analogues, benzimidazole-derived isotonitazene and its derivatives are the current NPS opioids of concern. Hence, in this study, we implement immunopharmacotherapy wherein antibodies are produced with high titers and nanomolar affinity to multiple benzimidazole-derived NPS opioids (BNO). Notably, these antibodies blunt psychoactive and physiological repercussions from BNO exposure, which was observed through antinociception, whole-body plethysmography, and blood-brain biodistribution studies. Moreover, we detail previously unreported pharmacokinetics of these drugs, which explains the struggle of traditional pharmaceutical opioid antagonists against BNO substances. These findings provide further insight into the in vivo effects of BNO drugs and the development of effective broad-spectrum therapeutics against NPS opioids.
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Analgésicos Opioides/inmunología , Bencimidazoles/inmunología , Drogas Ilícitas/inmunología , Vacunas Conjugadas/inmunología , Analgésicos Opioides/síntesis química , Analgésicos Opioides/farmacocinética , Animales , Bencimidazoles/síntesis química , Bencimidazoles/farmacocinética , Femenino , Haptenos/química , Haptenos/inmunología , Hemocianinas/química , Hemocianinas/inmunología , Drogas Ilícitas/síntesis química , Drogas Ilícitas/farmacocinética , Ratones Endogámicos BALB C , Nocicepción/efectos de los fármacos , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/prevención & control , Vacunas Conjugadas/químicaRESUMEN
BACKGROUND: Opioid-induced respiratory depression (OIRD) is a serious complication that can lead to negative outcomes. There are known risk factors for OIRD; however, a lack of national guidelines for the prevention and early detection of OIRD exists. METHODS: An evidence-based practice study was conducted to create an enhanced monitoring (EM) program. The EM program consisted of risk stratification of surgical spine patients, including the use of STOP-BANG screening for obstructive sleep apnea, capnography monitoring, use of home positive airway pressure therapy, capnography alarm optimization, hospitalist consultation, nursing education, and patient education. RESULTS: Approximately 17% (N = 937/5,462) of surgical spine patients were enrolled in the EM program. Fifty-six percent of EM patients were monitored with capnography and had out of range end-tidal carbon dioxide levels 17% of the time. The rate of transfers to the intensive care unit (ICU) for OIRD decreased, though not statistically significant (p = .151). CONCLUSIONS: The EM program with risk stratification was found to reduce transfers to the ICU for OIRD. Although not statistically significant, the decreased number of transfers was clinically significant. Engagement of the interprofessional team and capnography alarm parameter optimization helped to reduce nonactionable alarms.