Effect of lipid-lowering medications in patients with coronary artery bypass grafting surgery outcomes.

BACKGROUND: Increased life expectancy and improved medical technology allow increasing numbers of elderly patients to undergo cardiac surgery. Elderly patients may be at greater risk of postoperative morbidity and mortality. Complications can lead to worsened quality of life, shortened life expectancy and higher healthcare costs. Reducing perioperative complications, especially severe adverse events, is key to improving outcomes in patients undergoing cardiac surgery. The objective of this study is to determine whether perioperative lipid-lowering medication use is associated with a reduced risk of complications and mortality after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: After IRB approval, we reviewed charts of 9,518 patients who underwent cardiac surgery with CPB at three medical centers between July 2001 and June 2015. The relationship between perioperative lipid-lowering treatment and postoperative outcome was investigated. 3,988 patients who underwent CABG met inclusion criteria and were analyzed. Patients were divided into lipid-lowering or non-lipid-lowering treatment groups. RESULTS: A total of 3,988 patients were included in the final analysis. Compared to the patients without lipid-lowering medications, the patients with lipid-lowering medications had lower postoperative neurologic complications and overall mortality (P < 0.05). Propensity weighted risk-adjustment showed that lipid-lowering medication reduced in-hospital total complications (odds ratio (OR) = 0.856; 95% CI 0.781-0.938; P < 0.001); all neurologic complications (OR = 0.572; 95% CI 0.441-0.739; P < 0.001) including stroke (OR = 0.481; 95% CI 0.349-0.654; P < 0.001); in-hospital mortality (OR = 0.616; 95% CI 0.432-0.869; P = 0.006; P < 0.001); and overall mortality (OR = 0.723; 95% CI 0.634-0.824; P < 0.001). In addition, the results indicated postoperative lipid-lowering medication use was associated with improved long-term survival in this patient population. CONCLUSIONS: Perioperative lipid-lowering medication use was associated with significantly reduced postoperative adverse events and improved overall outcome in elderly patients undergoing CABG surgery with CPB.

Comparison of Oral Loading Dose to Intravenous Acetaminophen in Children for Analgesia After Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.

BACKGROUND: Acetaminophen is a frequently used adjunct analgesic in pediatric patients undergoing tonsillectomy and adenoidectomy. We compared opioid administration following preoperative intravenous (IV) or oral acetaminophen in addition to a standard multimodal regimen to test the hypothesis that 1 loading dose approach would provide superior opioid sparing effects among pediatric surgical patients undergoing tonsillectomy and adenoidectomy. METHODS: This single-center, double-blind, double-dummy prospective randomized study was conducted in patients ages 3 to 15 years undergoing tonsillectomy and adenoidectomy with or without myringotomy and tube placement between September 2017 and July 2019. Subjects received 1 dose of either oral acetaminophen 30 mg/kg with IV placebo (oral group) or IV acetaminophen 15 mg/kg with oral placebo (IV group). Acetaminophen plasma levels were measured at 2 timepoints to evaluate safety and determine plasma levels attained by each dosing regimen. Intraoperative opioid administration and postoperative analgesia were standardized. Standardized postoperative multimodal analgesia included opioid if needed to control pain assessed by standardized validated pediatric pain scales. The primary outcome measure was total opioid administration in the first 24 hours after surgery. Continuous data were not normally distributed and were analyzed using the Wilcoxon rank sum test and the Hodges-Lehman estimator of the median difference. Clinical significance was defined as a 100 µg/kg IV morphine equivalents per day difference. RESULTS: Sixty-six subjects were randomized into and completed the study (29 women, 37 men; age 5.9 ± 3.0 years; percentile weight for age 49.5 ± 30.2; no differences between groups). There was no opioid dose difference between oral (median 147.6; interquartile range [IQR], 119.6-193.0 µg/kg) and IV groups (median 125.4; IQR, 102.8-150.9 µg/kg; median difference 21.3; 95% confidence interval [CI] -2.5 to 44.2 µg/kg IV morphine equivalents; P = .13). No acetaminophen levels exceeded the predefined safety threshold (40 mg/L). No difference was found in the percentage of patients with severe pain: 50.0% oral group, 47.2% IV group; relative risk of severe pain in IV 0.94; 95% CI, 0.57-1.6; P = .82. Postoperative plasma acetaminophen levels were higher in oral (22; IQR, 16-28 mg/L) than IV (20; IQR, 17-22 mg/L) group (median difference 7.0; 4.0-8.0 mg/L; P = .0001). CONCLUSIONS: Opioid-sparing effects did not differ following an oral or standard IV acetaminophen loading dose with no identified acetaminophen toxicity in pediatric patients undergoing tonsillectomy and adenoidectomy who received standardized multimodal postoperative analgesia. An oral loading dose may provide more consistent serum acetaminophen levels at lower cost compared to a standard IV dose.

Course of illness and outcomes in older COVID-19 patients treated with HFNC: a retrospective analysis.

Coronavirus disease-2019 (COVID-19) has rapidly spread worldwide and causes high mortality of elderly patients. High-flow nasal cannula therapy (HFNC) is an oxygen delivery method for severely ill patients. We retrospectively analyzed the course of illness and outcomes in 110 elderly COVID-19 patients (≥65 years) treated with HFNC from 6 hospitals. 38 patients received HFNC (200 mmHg < PaO2/FiO2 ≤ 300 mmHg, early HFNC group), and 72 patients received HFNC (100 mmHg < PaO2/FiO2 ≤ 200 mmHg, late HFNC group). There were no significant differences of sequential organ failure assessment (SOFA) scores and APECH II scores between early and late HFNC group on admission. Compared with the late HFNC group, patients in the early HFNC group had a lower likelihood of developing severe acute respiratory distress syndrome (ARDS), longer time from illness onset to severe ARDS and shorter duration of viral shedding after illness onset, as well as shorter lengths of ICU and hospital stay. 24 patients died during hospitalization, of whom 22 deaths (30.6%) were in the late HFNC group and 2 (5.3%) in the early HFNC group. The present study suggested that the outcomes were better in severely ill elderly patients with COVID-19 receiving early compared to late HFNC.

Perioperative dexmedetomidine and 5-year survival in patients undergoing cardiac surgery.

BACKGROUND: Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery. METHODS: This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 µg kg-1 min-1 was initiated before or immediately after cardiopulmonary bypass and lasted for < 24 h. The primary outcome was 5-year survival after cardiac surgery. The propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting approaches were used to minimise bias. Survival analyses were performed with Cox proportional-hazard models. RESULTS: The median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P<0.001), and after adjustment with PSM (HR=0.63; 95% CI, 0.45-0.89; P=0.009), IPTW (HR=0.70; 95% CI, 0.51-0.95; P=0.023), or overlap weighting (HR=0.67; 95% CI, 0.51-0.89; P=0.006). The 5-yr mortality rate after cardiac surgery was 13% and 20% in the dexmedetomidine and non-dexmedetomidine groups, respectively (PSM adjusted odds ratio=0.61; 95% CI, 0.42-0.89; P=0.010). CONCLUSION: Perioperative dexmedetomidine infusion was associated with improved 5-yr survival in patients undergoing cardiac surgery.

Simultaneous comparison of depth of sedation performance between SedLine and BIS during general anesthesia using custom passive interface hardware: study protocol for a prospective, non-blinded, non-randomized trial.

BACKGROUND: Intraoperative brain function monitoring with processed electroencephalogram (EEG) indices, such as the bispectral index (BIS) and patient state index (PSI), may improve characterization of the depth of sedation or anesthesia when compared to conventional physiologic monitors, such as heart rate and blood pressure. However, the clinical assessment of anesthetic depth may not always agree with available processed EEG indices. To concurrently compare the performance of BIS and SedLine monitors, we present a data collection system using shared individual generic sensors connected to a custom-built passive interface box. METHODS: This prospective, non-blinded, non-randomized study will enroll 100 adult American Society of Anesthesiologists (ASA) class I-III patients presenting for elective procedures requiring general anesthesia. BIS and SedLine electrodes will be placed preoperatively according to manufacturer recommendations and their respective indices tracked throughout anesthesia induction, maintenance and emergence. The concordance between processed EEG indices and clinical assessments of anesthesia depth will be analyzed with chi-square and kappa statistic. DISCUSSION: Prior studies comparing brain function monitoring devices have applied both sensors on the forehead of study subjects simultaneously. With limited space and common sensor locations between devices, it is not possible to place both commercial sensor arrays according to the manufacturer's recommendations, thus compromising the validity of these comparisons. This trial utilizes a custom interface allowing signals from sensors to be shared between BIS and SedLine monitors to provide an accurate comparison. Our results will also characterize the degree of agreement between processed EEG indices and clinical assessments of anesthetic depth as determined by the anesthesiologists' interpretations of acute changes in blood pressure and heart rate as well as the administration, or change to the continuous delivery, of medications at these timepoints. Patient factors (such as burst suppression state or low power EEG conditions from aging brain), surgical conditions (such as use of electrocautery), artifacts (such as electromyography), and anesthesia medications and doses (such as end-tidal concentration of volatile anesthetic or hypnotic infusion dose) that lead to lack of agreement will be explored as well. TRIAL REGISTRATION: Clinical Trials ( ClinicalTrials.gov ), NCT03865316 . Registered on 4 February 2019 - retrospectively registered. SPONSOR: Masimo Corporation.

Frailty, Race/Ethnicity, Functional Status, and Adverse Outcomes After Total Hip/Knee Arthroplasty: A Moderation Analysis.

BACKGROUND: Although frailty has been shown to be associated with adverse outcomes in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), prior studies have not examined how race/ethnicity might moderate these associations. We aimed to assess race/ethnicity as a potential moderator of the associations of frailty and functional status with arthroplasty outcomes. METHODS: The National Surgical Quality Improvement Program was queried for patients who underwent THA or TKA from 2011 to 2017. Frailty was assessed using the modified frailty index. Regression analyses were conducted to examine associations connecting frailty/functional status with 30-day readmission, adverse discharge, and length of stay (LOS). Further analyses were conducted to investigate race/ethnicity as a potential moderator of these relationships. RESULTS: We identified 219,143 TKA and 130,022 THA patients. Frailty and nonindependent functional status were positively associated with all outcomes (P < .001). Compared to White non-Hispanic patients, Black non-Hispanic patients had higher odds for all outcomes after TKA (P < .001) and for adverse discharge/longer LOS after THA (P < .001). Similar associations were observed for Hispanics for the adverse discharge/LOS outcomes. Race/ethnicity moderated the effects of frailty in TKA for all outcomes and in THA for adverse discharge/LOS. Race/ethnicity moderated the effects of nonindependent function in TKA for adverse discharge/LOS and on LOS alone for THA. CONCLUSION: Disparities for Black non-Hispanic and Hispanic patients persist for readmission, adverse discharge, and LOS. However, the effects of increasing frailty and nonindependent functional status on these outcomes were the most pronounced among White non-Hispanic patients.

Oxygen Reserve Index: Utility as an Early Warning for Desaturation in High-Risk Surgical Patients.

BACKGROUND: Perioperative pulse oximetry hemoglobin saturation (Spo2) measurement is associated with fewer desaturation and hypoxia episodes. However, the sigmoidal nature of oxygen-hemoglobin dissociation limits the accuracy of estimation of the partial pressure of oxygen (Pao2) >80 mm Hg and correspondingly limits the ability to identify when Pao2 >80 mm Hg but falling. We hypothesized that a proxy measurement for oxygen saturation (Oxygen Reserve Index [ORI]) derived from multiwavelength pulse oximetry may allow additional warning time before critical desaturation or hypoxia. To test our hypothesis, we used a Masimo multiwavelength pulse oximeter to compare ORI and Spo2 warning times during apnea in high-risk surgical patients undergoing cardiac surgery. METHODS: This institutional review board-approved prospective study (NCT03021473) enrolled American Society of Anesthesiologists physical status III or IV patients scheduled for elective surgery with planned preinduction arterial catheter placement. In addition to standard monitors, an ORI sensor was placed and patients were monitored with a pulse oximeter displaying the ORI, a nondimensional parameter that ranges from 0 to 1. Patients were then preoxygenated until ORI plateaued. Following induction of anesthesia, mask ventilation with 100% oxygen was performed until neuromuscular blockade was established. Endotracheal intubation was accomplished using videolaryngoscopy to confirm placement. The endotracheal tube was not connected to the breathing circuit, and patients were allowed to be apneic. Ventilation was resumed when Spo2 reached 94%. We defined ORI warning time as the time from when the ORI alarm registered (based on the absolute value and the rate of change) until the Spo2 decreased to 94%. We defined the Spo2 warning time as the time for Spo2 to decrease from 97% to 94%. The added warning time provided by ORI was defined as the difference between ORI warning time and Spo2 warning time. RESULTS: Forty subjects were enrolled. Complete data for analysis were available from 37 patients. The ORI alarm registered before Spo2 decreasing to 97% in all patients. Median (interquartile range [IQR]) ORI warning time was 80.4 seconds (59.7-105.9 seconds). Median (IQR) Spo2 warning time was 29.0 seconds (20.5-41.0 seconds). The added warning time provided by ORI was 48.4 seconds (95% confidence interval [CI], 40.4-62.0 seconds; P < .0001). CONCLUSIONS: In adult high-risk surgical patients, ORI provided clinically relevant added warning time of impending desaturation compared to Spo2. This additional time may allow modification of airway management, earlier calls for help, or assistance from other providers. The potential patient safety impact of such monitoring requires further study.

Remote Ischemic Pre-conditioning in Subarachnoid Hemorrhage: A Prospective Pilot Trial.

BACKGROUND: Cerebral injury from aneurysmal subarachnoid hemorrhage (aSAH) is twofold. The initial hemorrhage causes much of the injury; secondary injury can occur from delayed cerebral ischemia (DCI). Remote ischemic preconditioning (RIPC) is a mechanism of organ protection in response to transient ischemia within a distant organ. This pilot trial sought to apply RIPC in patients with aSAH to evaluate its effect on secondary cerebral injury and resultant outcomes. METHODS: Patients were randomized to the high-pressure occlusion group (HPO) or the low-pressure occlusion group (LPO). Lower extremity RIPC treatment was initiated within 72 h of symptom onset and every other day for 14 days or until Intensive Care Unit (ICU) discharge. In HPO, each treatment consisted of 4 five-minute cycles of manual blood pressure cuff inflation with loss of distal pulses. LPO received cuff inflation with lower pressures while preserving distal pulses. Retrospectively matched controls were also analyzed. Efficacy of treatment was measured by total days spent in vasospasm out of study enrollment days, hospital and ICU length of stay (LOS), cerebral infarction, one and six month modified Rankin score, and mortality. RESULTS: The final analysis included 33 patients with 11 in each group. Patient demographics, aneurysm location, admission airway status, Glasgow Coma Scale (GCS), modified Rankin score, Hunt and Hess score, modified Fisher Score and aneurysm management were not significantly different between groups. Hospital and ICU LOS was shorter in LPO compared to the control (p = 0·0468 and p = 0·0409, respectively). Total vasospasm days/study enrollment days, cerebral infarction, one and six month modified Rankin score, and mortality were not significantly different between the groups. CONCLUSIONS: This pilot trial did demonstrate feasibility and safety. The shortened LOS in the LPO may implicate a protective role of RIPC and warrants future study.

Study of early warning for desaturation provided by Oxygen Reserve Index in obese patients.

Acute hemoglobin desaturation can reflect rapidly decreasing PaO2. Pulse oximetry saturation (SpO2) facilitates hypoxia detection but may not significantly decrease until PaO2 < 80 mmHg. The Oxygen Reserve Index (ORI) is a unitless index that correlates with moderately hyperoxic PaO2. This study evaluated whether ORI provides added arterial desaturation warning in obese patients. This IRB approved, prospective, observational study obtained written informed consent from Obese (body mass index (BMI) kg m-2; 30 < BMI < 40) and Normal BMI (19 < BMI < 25) adult patients scheduled for elective surgery requiring general endotracheal anesthesia. Standard monitors and an ORI sensor were placed. Patient's lungs were pre-oxygenated with 100% FiO2. After ORI plateaued, general anesthesia was induced, and endotracheal intubation accomplished using a videolaryngoscope. Patients remained apneic until SpO2reached 94%. ORI and SpO2 were recorded continuously. Added warning time was defined as the difference between the time to SpO2 94% from ORI alarm start or from SpO2 97%. Data are reported as median; 95% confidence interval. Complete data were collected in 36 Obese and 36 Normal BMI patients. ORI warning time was always longer than SpO2 warning time. Added warning time provided by ORI was 46.5 (36.0-59.0) seconds in Obese and 87.0 (77.0-109.0) seconds in Normal BMI patients, and was shorter in Obese than Normal BMI patients difference 54.0 (38.0-74.0) seconds (p < 0.0001). ORI provided what was felt to be clinically significant added warning time of arterial desaturation compared to SpO2. This added time might allow earlier calls for help, assistance from other providers, or modifications of airway management.Trial registration ClinicalTrials.gov NCT03021551.

Perioperative Dexmedetomidine Improves Outcomes of Kidney Transplant.

Graft function is crucial for successful kidney transplantation. Many factors may affect graft function or cause delayed graft function (DGF), which decreases the prognosis for graft survival. This study was designed to evaluate whether the perioperative use of dexmedetomidine (Dex) could improve the incidence of function of graft kidney and complications after kidney transplantation. A total of 780 patients underwent kidney transplantations, 315 received intravenous Dex infusion during surgery, and 465 did not. Data were adjusted with propensity scores and multivariate logistic regression was used. The primary outcomes are major adverse complications, including DGF and acute rejection in the early post-transplantation phase. The secondary outcomes included length of hospital stay (LOS), infection, overall complication, graft functional status, post-transplantation serum creatinine values, and estimated glomerular filtration rate (eGFR). Dex use significantly decreased DGF (19.37% vs. 23.66%; adjusted odds ratio, 0.744; 95% confidence interval, 0.564-0.981; P = 0.036), risk of infection, risk of acute rejection in the early post-transplantation phase, the risk of overall complications, and LOS. However, there were no statistical differences in 90-day graft functional status or 7-day, 30-day, and 90-day eGFR. Perioperative Dex use reduced incidence of DGF, risk of infection, risk of acute rejection, overall complications, and LOS in patients who underwent kidney transplantation.

Impact of preoperative pectoralis plane nerve blocks for mastectomy on perioperative opioid consumption: a retrospective study.

Aim: To compare perioperative opioid consumption for patients undergoing mastectomy surgery with or without pectoralis nerve (PECS) plane blocks. Patients & methods: Retrospective study evaluating 152 adult females with mastectomies. Demographics, postanesthesia care unit stay duration and opioid consumption data at three time points were collected and analyzed for statistical significance. Results: 98 patients were included in the PECS block group, 54 patients were in the general anesthesia only group. Age and BMI were comparable. Total perioperative intravenous opioid consumption was less in the PECS block group (50.88 mg) compared with the general anesthesia only group (67.83 mg), p < 0.001. Conclusion: Acute pain after mastectomy is often severe. PECS plane block may decrease perioperative opioid consumption after mastectomy surgery compared with general anesthesia alone.

Effect of Dexmedetomidine on Cardiac Surgery-Associated Acute Kidney Injury: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials.

OBJECTIVE: Cardiac surgery-associated acute kidney injury (CS-AKI) is associated with high mortality rates. This study aimed to determine the effects of perioperative dexmedetomidine (DEX) administration on CS-AKI in adult patients. DESIGN: A meta-analysis with trial sequential analysis of randomized controlled trials. SETTING: PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases were searched up to March 11, 2019 for relevant articles. The study protocol was registered at the International Prospective Register of Systematic Reviews (registration number: CRD42019128139). PARTICIPANTS: Adult patients undergoing cardiac surgery. INTERVENTIONS: Dexmedetomidine compared with controls. MEASUREMENTS AND MAIN RESULTS: Nine randomized controlled trials with a total of 1,308 patients were included. Use of DEX significantly reduced the incidence of CS-AKI (risk ratio = 0.60, 95% confidence interval = 0.41-0.87, p = 0.008, I2 = 30%), without significant publication bias. The trial sequential analysis result suggested that there was enough evidence for this outcome. Sensitivity analysis confirmed the robustness of the result. The improvement of CS-AKI was primarily significant in preoperative and/or intraoperative administration of DEX with or without postoperative continuation, patients with age ≥60 years, and studies with low risk of bias. The subgroup analysis did not show statistical differences. Dexmedetomidine use also was associated with less prolonged ventilation and lower incidences of pulmonary complications and delirium postoperatively. The level of evidence was high for the incidence of CS-AKI on the Grading of Recommendations Assessment, Development and Evaluation profile. CONCLUSION: Perioperative DEX administration provided protective effects against CS-AKI, especially when initiated before and during surgery in elderly patients.

Retrospective Cohort Study on the Optimal Timing of Orogastric Tube/Nasogastric Tube Insertion in Infants With Pyloric Stenosis.

BACKGROUND: Hypertrophic pyloric stenosis in infants can cause a buildup of gastric contents. Orogastric tubes (OGTs) or nasogastric tubes (NGTs) are often placed in patients with pyloric stenosis before surgical management to prevent aspiration. However, exacerbation of gastric losses may lead to electrolyte abnormalities that can delay surgery, and placement has been associated with increased risk of postoperative emesis. Currently, there are no evidence-based guidelines regarding OGT/NGT placement in these patients. This study examines whether OGT/NGT placement before arrival in the operating room was associated with a longer time to readiness for surgery as defined by normalization of electrolytes. Secondary outcomes included time from surgery to discharge and ability to tolerate feeds by 6 hours postoperatively in patients with and without early OGT/NGT placement. METHODS: In this multicenter retrospective cohort study, data were extracted from the medical records of 481 patients who underwent pyloromyotomy for infantile hypertrophic pyloric stenosis from March 2013 to June 2016. Multivariable linear regression and Cox proportional hazard models were constructed to evaluate the association between placement of an OGT/NGT at the time of admission with increased time to readiness for surgery (defined as the time from admission to the first set of normalized laboratory values) and increased time from surgery to discharge. Multivariable logistic regression was used to evaluate the association between early OGT/NGT placement and the ability to tolerate oral intake at 6 hours postsurgery. Analyses were adjusted for site differences. RESULTS: Among patients admitted with electrolyte abnormalities, those with an OGT/NGT placed on presentation required more time until their serum electrolytes were at acceptable levels for surgery by regression analysis (19.2 hours difference; 95% confidence interval, 10.05-28.41; P < .001), after adjusting for site. Overall, patients who had OGTs/NGTs placed before presentation in the operating room had a longer length of stay from surgery to discharge than those without (38.8 hours difference; 95% confidence interval, 25.35-52.31; P < .001), after adjusting for site. OGT/NGT placement before surgery was not associated with failure to tolerate oral intake within 6 hours of surgery after adjusting for site, corrected gestational age, and baseline serum electrolytes. CONCLUSIONS: OGT/NGT placement on admission for pyloric stenosis is associated with a longer time to electrolyte correction in infants with abnormal laboratory values on presentation and, subsequently, a longer time until they are ready for surgery. It is also associated with longer postoperative hospital stay but not an increased risk of feeding intolerance within 6 hours of surgical repair.

A comparison of postoperative outcomes with PDA ligation in the OR versus the NICU: a retrospective cohort study on the risks of transport.

BACKGROUND: Although patent ductus arteriosus (PDA) ligations in the Neonatal Intensive Care Unit (NICU) have been an accepted practice, many are still performed in the Operating Room (OR). Whether avoiding transport leads to improved perioperative outcomes is unclear. Here we aimed to determine whether PDA ligations in the NICU corresponded to higher risk of surgical site infection or mortality and if transport was associated with worsened perioperative outcomes. METHODS: We performed a retrospective cohort study of NICU patients, ≤37 weeks post-menstrual age, undergoing surgical PDA ligation in the NICU or OR. We excluded any infants undergoing device PDA closure. We measured the incidence of perioperative hypothermia, cardiac arrest, decreases in SpO2, hemodynamic instability and postoperative surgical site infection, sepsis and mortality. RESULTS: Data was collected on 189 infants (100 OR, 89 NICU). After controlling for number of preoperative comorbidities, weight at time of procedure, procedure location and hospital in the mixed-effect model, no significant difference in mortality or sepsis was found (odds ratio 0.31, 95%CI 0.07, 1.30; p = 0.107, and odds ratio 0.40; 95%CI 0.14, 1.09; p = 0.072, respectively). There was an increased incidence of hemodynamic instability on transport postoperatively in the OR group (12.4% vs 2%, odds ratio 6.93; 95% CI 1.48, 35.52; p = 0.014). CONCLUSION: PDA ligations in the NICU were not associated with higher incidences of surgical site infection or mortality. There was an increased incidence of hemodynamic instability in the OR group on transport back to the NICU. Larger multicenter studies following long-term outcomes are needed to evaluate the safety of performing all PDA ligations in the NICU.

Inhalation of high concentration hydrogen gas improves short-term outcomes in a rat model of asphyxia induced-cardiac arrest.

Cardiogenic global brain hypoxia-ischemia is a devastating medical problem that is associated with unfavorable neurologic outcomes. Low dose hydrogen gas (up to 2.9%) has been shown to be neuroprotective in a variety of brain diseases. In the present study, we investigated the protective effect of water by electrolysis-derived high concentration hydrogen gas (60%) in a rat model of asphyxia induced-cardiac arrest and global brain hypoxia-ischemia. High concentration hydrogen gas was either administered starting 1 hour prior to cardiac arrest for 1 hour and starting 1 hour post-resuscitation for 1 hour (pre- & post-treatment) or starting 1 hour post-resuscitation for 2 hours (post-treatment). In animals subjected to 9 minutes of asphyxia, both therapeutic regimens tended to reduce the incidence of seizures and neurological deficits within 3 days post-resuscitation. In rats subjected to 11 minutes of asphyxia, significantly worse neurological deficits were observed compared to 9 minutes asphyxia, and pre- & post-treatment had a tendency to improve the success rate of resuscitation and to reduce the seizure incidence within 3 days post-resuscitation. Findings of this preclinical study suggest that water electrolysis-derived 60% hydrogen gas may improve short-term outcomes in cardiogenic global brain hypoxia-ischemia.

A comparison of midazolam and zolpidem as oral premedication in children, a prospective randomized double-blinded clinical trial.

BACKGROUND: Anxiety associated with pediatric surgery can be stressful. Midazolam is a well-accepted anxiolytic in this setting. However, there are cases in which this medication is not effective. Zolpidem is a short-acting nonbenzodiazepine hypnotic drug that is administered orally and has quick onset of action (~15 minutes), and 2-3 hour duration. AIMS: Based on the theory that impaired perception following oral zolpidem administration would suppress the development of anxiety, we sought to compare zolpidem to midazolam for pediatric preoperative anxiety. METHODS: This prospective randomized double-blinded clinical trial was designed to compare the effectiveness of oral midazolam and zolpidem for anxiety premedication. Eighty ASA class I-II pediatric patients between 2 and 9 years old, surgery >2 hours, and at least 23 hours postoperative admission were included in the study. Randomization was done with 0.5 mg/kg midazolam or 0.25 mg/kg zolpidem administered orally. The primary outcome measure was between group difference in patient anxiety at the time of separation using the Modified Yale Preoperative Anxiety Scale. Secondary outcomes included emergence delirium and mask acceptance at induction. RESULTS: There was no significant difference in Modified Yale Preoperative Anxiety Scale scores at separation between midazolam (median/interquartile range = 26.7/23.3-36.6) and zolpidem (median/interquartile range = 30.0/23.3-56.6) groups, difference 0.01 (95% CI -3E-5 , 3E-2 ; P = 0.07). Mask acceptance score was significantly better in the midazolam group. There was no significant difference in emergence delirium scores between groups. CONCLUSION: This study demonstrates that zolpidem, as dosed, was similar to midazolam with regard to anxiety scoring, and inferior with regard to mask acceptance scores.

Remote Limb Ischemic Preconditioning Attenuates Cerebrovascular Depression During Sinusoidal Galvanic Vestibular Stimulation via α1-Adrenoceptor-Protein Kinase Cε-Endothelial NO Synthase Pathway in Rats.

BACKGROUND: Vasovagal syncope (VVS) is characterized by hypotension and bradycardia followed by lowering of cerebral blood flow. Remote limb ischemic preconditioning (RIPC) is well documented to provide cardio- and neuroprotection as well as to improve cerebral blood flow. We hypothesized that RIPC will provide protection against VVS-induced hypotension, bradycardia, and cerebral hypoperfusion. Second, because endothelial nitric oxide synthase has been reported as a mediator of cerebral blood flow control, we hypothesized that the mechanism by which RIPC primes the vasculature against VVS is via the α1-adrenoceptor-protein kinase Cε-endothelial nitric oxide synthase pathway. METHODS AND RESULTS: We utilized sinusoidal galvanic vestibular stimulation in rats as a model of VVS. RIPC attenuated the lowerings of mean arterial pressure, heart rate, and cerebral blood flow caused by sinusoidal galvanic vestibular stimulation, as well as improving behavior during, and recovery after, stimulation. RIPC induced elevated serum norepinephrine, increased expression of brain α1-adrenoceptors, and reduced brain expression of norepinephrine transporter 1. Antagonizing adrenoceptors and norepinephrine transporter 1 prevented RIPC protection of cerebral perfusion during sinusoidal galvanic vestibular stimulation. CONCLUSIONS: Taken together, this study indicates that RIPC may be a potential therapy that can prevent VVS pathophysiology, decrease syncopal episodes, and reduce the injuries associated with syncopal falls. Furthermore, the α1-adrenoceptor-protein kinase Cε-endothelial nitric oxide synthase pathway may be a therapeutic target for regulating changes in cerebral blood flow.

Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research.

Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments.