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.

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.

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.

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.

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.

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.

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.

Sedation After Cardiac Surgery: Is One Drug Better Than Another?

The classic high-dose narcotic-based cardiac anesthetic has been modified to facilitate a fast-track, rapid recovery in the intensive care unit (ICU). Postoperative sedation is consequently now an essential component in recovery of the patient undergoing cardiac surgery. It must facilitate the patient's unawareness of the environment as well as reduce the discomfort and anxiety caused by surgery, intubation, mechanical ventilation, suction, and physiotherapy. Benzodiazepines seem well suited for this role, but propofol, opioids, and dexmedetomidine are among other agents commonly used for sedation in the ICU. However, what is an ideal sedative for this application? When compared with benzodiazepine-based sedation regimens, nonbenzodiazepines have been associated with shorter duration of mechanical ventilation and ICU length of stay. Current sedation guidelines recommend avoiding benzodiazepine use in the ICU. However, there are no recommendations on which alternatives should be used. In postcardiac surgery patients, inotropes and vasoactive medications are often required because of the poor cardiac function. This makes sedation after cardiac surgery unique in comparison with the requirements for most other ICU patient populations. We reviewed the current literature to try to determine if 1 sedative regimen might be better than others; in particular, we compare outcomes of propofol and dexmedetomidine in postoperative sedation in the cardiac surgical ICU.

Use of Esophageal Hemoximetry to Assess the Effect of Packed Red Blood Cell Transfusion on Gastrointestinal Oxygenation in Newborn Infants.

Objectives There are no widely accepted methods of continuously monitoring gut oxygenation in the newborn during packed red blood cell transfusion. We investigated the use of an orally inserted light spectroscopy probe to measure lower esophageal oxyhemoglobin saturations (eStO2) before, during, and after transfusion and made comparisons with abdominal near-infrared spectroscopy (NIRS) and superior mesenteric artery (SMA) flow. Study Design Thirteen neonates with corrected gestational ages ranging from 22 weeks, 0 day to 37 weeks, 5 days were enrolled. eStO2 and NIRS measurements were recorded continuously for a 25-hour period starting 1 hour prior to starting the 4-hour transfusion. Transabdominal ultrasound was used to measure SMA flow prior to, upon completion, and 20 hours after the transfusion. Results Twelve infants completed the study. eStO2 was well-tolerated and was weakly (r = 0.06) correlated (p < 0.001) with NIRS. Compared with NIRS, eStO2 demonstrated a markedly greater variation in oxyhemoglobin values. NIRS and SMA flow measurements did not change, while eStO2 increased from 48 ± 5% and 45 ± 5% in the pre- and intratransfusion periods to 57 ± 4% in the posttransfusion period (p = 0.03). Conclusion Measurement of eStO2 is feasible in neonates and may provide a continuous and sensitive index of rapid changes in mesenteric oxygenation in this patient population.

Comparison of the GlideScope Cobalt® and Storz DCI® Video Laryngoscopes in Children Younger Than 2 Years of Age During Manual In-Line Stabilization: A Randomized Trainee Evaluation Study.

OBJECTIVES: Video laryngoscopy facilitates tracheal intubation during manual in-line stabilization in adults, but it is not clear whether these findings translate to children. We compared trainee intubation times obtained using the GlideScope Cobalt® and Storz DCI® video laryngoscopes versus direct laryngoscopy in young children with immobilized cervical spines. METHODS: Ninety-three children younger than 2 years underwent laryngoscopy with manual in-line stabilization using direct laryngoscopy, GlideScope Cobalt® video laryngoscopy, or Storz DCI® video laryngoscopy. Laryngoscopists were anesthesiology trainees in postgraduate training year of 3 or more. Total time to successful intubation (TTSI), best glottic view, and maximum degrees of neck deviation were recorded. An intubation time difference longer than 10 seconds was defined as clinically significant. RESULTS: Data are reported as median; 95% confidence interval. The TTSI was similar among groups although Storz times were longer (median, 33.3 seconds; 95% confidence interval, 26.2-43.3 seconds) when compared to direct laryngoscopy (median, 23.3 seconds; 95% confidence interval, 20.7-26.5 seconds; P = 0.02). Obtaining a grade 1 Cormack-Lehane glottic view was less likely with direct laryngoscopy (P = 0.002). Maximum degrees of neck deviation were: Storz (median, 2.0; 95% confidence interval, 1.2-2.8), GlideScope (median, 2.0; 95% confidence interval, 1.4-2.6), and direct laryngoscopy (median, 1.9; 95% confidence interval, 1.2-2.1; P = 0.48). CONCLUSIONS: Trainees were able to safely perform tracheal intubation in children younger than 2 years using any of the studied laryngoscopes, although Storz use resulted in a longer TTSI when compared to direct laryngoscopy. Video laryngoscopy may enhance best Cormack-Lehane glottic view during manual in-line cervical spine immobilization, but additional technical skills are needed to successfully complete tracheal intubation.

Phosphoinositide 3-Kinase Gamma Contributes to Neuroinflammation in a Rat Model of Surgical Brain Injury.

Neuroinflammation plays an important role in the pathophysiology of surgical brain injury (SBI). Phosphoinositide 3-kinase gamma (PI3Kγ), predominately expressed in immune and endothelial cells, activates multiple inflammatory responses. In the present study, we investigated the role of PI3Kγ and PI3Kγ-activated phosphodiesterase 3B (PDE3B) in neuroinflammation in a rat model of SBI. One hundred and fifty-two male Sprague Dawley rats (weight 280-350 g) were subjected to a partial right frontal lobe corticotomy model of SBI. A PI3Kγ pharmacological inhibitor (AS252424 or AS605240) was administered intraperitoneally. PI3Kγ siRNA, human recombinant active-PI3Kγ protein, or human recombinant active-PDE3B protein were administered intracerebroventricularly. Post-SBI assessments included neurobehavioral tests, brain water content, Western blot, and immunohistochemistry. Endogenous PI3Kγ levels were increased within peri-resection brain tissues after SBI, accompanied by increased brain water content and neurological functional deficits. There was a trend toward increased endogenous PDE3B phosphorylation after SBI. The selective PI3Kγ inhibitors AS252424 and AS605240 reduced brain water content surrounding corticotomy and improved neurological function after SBI. SBI increased and PI3Kγ inhibitor decreased levels of myeloperoxidase, cluster of differentiation 3, mast cell degranulation, E-selectin, and IL-1 in peri-resection brain tissues. Direct administration of human recombinant active-PI3Kγ protein and active-PDE3B protein countered the protective effect of AS252424. PI3Kγ siRNA reduced PI3Kγ levels, decreased brain water content within peri-resection brain tissues, and improved neurological function after SBI. Collectively, our findings suggest that PI3Kγ contributed to neuroinflammation after SBI. The use of selective PI3Kγ inhibitors may be a novel approach to ameliorating SBI via their anti-inflammation effects. Significance statement: Life-saving or elective neurosurgeries often involve unavoidable damages to neighboring, nondiseased brain tissues. Such surgical brain injury (SBI) is attributable exclusively to the neurosurgical procedure itself and may cause postoperative complications that exacerbate neurological function. Although the importance of this medical problem is fully acknowledged, intraoperative administration of adjunctive treatment such as steroids and mannitol to patients undergoing neurosurgery appear not to be efficient remedies for SBI. To date, the issue of perioperative neuroprotection specifically against SBI has not been well studied. Using a clinically relevant rat model of SBI, we are exploring a new neuroprotective strategy targeting phosphoinositide 3-kinase gamma (PI3Kγ). PI3Kγ activates multiple inflammatory responses. By attenuating neuroinflammation, selective PI3Kγ inhibition would limit postoperative complications and benefit neurological outcomes.

The Relationship Between Oxygen Reserve Index and Arterial Partial Pressure of Oxygen During Surgery.

BACKGROUND: The use of intraoperative pulse oximetry (SpO2) enhances hypoxia detection and is associated with fewer perioperative hypoxic events. However, SpO2 may be reported as 98% when arterial partial pressure of oxygen (PaO2) is as low as 70 mm Hg. Therefore, SpO2 may not provide advance warning of falling arterial oxygenation until PaO2 approaches this level. Multiwave pulse co-oximetry can provide a calculated oxygen reserve index (ORI) that may add to information from pulse oximetry when SpO2 is >98%. This study evaluates the ORI to PaO2 relationship during surgery. METHODS: We studied patients undergoing scheduled surgery in which arterial catheterization and intraoperative arterial blood gas analysis were planned. Data from multiple pulse co-oximetry sensors on each patient were continuously collected and stored on a research computer. Regression analysis was used to compare ORI with PaO2 obtained from each arterial blood gas measurement and changes in ORI with changes in PaO2 from sequential measurements. Linear mixed-effects regression models for repeated measures were then used to account for within-subject correlation across the repeatedly measured PaO2 and ORI and for the unequal time intervals of PaO2 determination over elapsed surgical time. Regression plots were inspected for ORI values corresponding to PaO2 of 100 and 150 mm Hg. ORI and PaO2 were compared using mixed-effects models with a subject-specific random intercept. RESULTS: ORI values and PaO2 measurements were obtained from intraoperative data collected from 106 patients. Regression analysis showed that the ORI to PaO2 relationship was stronger for PaO2 to 240 mm Hg (r = 0.536) than for PaO2 over 240 mm Hg (r = 0.0016). Measured PaO2 was ≥100 mm Hg for all ORI over 0.24. Measured PaO2 was ≥150 mm Hg in 96.6% of samples when ORI was over 0.55. A random intercept variance component linear mixed-effects model for repeated measures indicated that PaO2 was significantly related to ORI (ß[95% confidence interval] = 0.002 [0.0019-0.0022]; P < 0.0001). A similar analysis indicated a significant relationship between change in PaO2 and change in ORI (ß [95% confidence interval] = 0.0044 [0.0040-0.0048]; P < 0.0001). CONCLUSIONS: These findings suggest that ORI >0.24 can distinguish PaO2 ≥100 mm Hg when SpO2 is over 98%. Similarly, ORI > 0.55 appears to be a threshold to distinguish PaO2 ≥150 mm Hg. The usefulness of these values should be evaluated prospectively. Decreases in ORI to near 0.24 may provide advance indication of falling PaO2 approaching 100 mm Hg when SpO2 is >98%. The clinical utility of interventions based on continuous ORI monitoring should be studied prospectively.

Intraoperative Red Blood Cell Transfusion in Infant Heart Transplant Patients Is Not Associated with Worsened Outcomes.

BACKGROUND: Red blood cell (RBC) transfusion is common during infant cardiac surgery. A previous report of pediatric heart transplant recipients showed that increased RBC transfusion volume was independently associated with increased length of intensive care unit stay. It is unclear whether transfusion to infants as a subgroup carries similar risks. This study investigated relationships between intraoperative RBC transfusion during heart transplantation and postoperative length of stay (LOS), morbidity, and mortality in infants. METHODS: Retrospective analysis of medical records from infants <1 year old undergoing primary heart transplantation at Loma Linda University Medical Center from 1985 to 2012 was conducted. Exclusion criteria included preoperative exchange transfusion or extracorporeal membrane oxygenation. Data sought included patient characteristics; intraoperative RBC transfusion volume and cardiopulmonary bypass details; and postoperative vasoactive support, ventilator support, morbidity, LOS, and 30-day mortality. The relationship of RBC transfusion volume (mL/kg) to these postoperative variables was assessed by univariate analysis. Multiple regression analysis of postoperative LOS included variables that were independent predictors of LOS or associated with ≥10% change in the ß-estimate for RBC effect. RESULTS: Data from 307 infants showed that most (66.8%) had single-ventricle physiology. Median age at transplant was 50 days, weight 3.95 kg, and intraoperative transfusion volume 109 mL/kg. Transfusion volume was inversely related to age and weight. Median postoperative LOS was 18.2 days. Univariate linear regression analysis of transfused volume showed no relationship to log-transformed postoperative LOS (F(1,305) = 0.00; P = 0.960; R = 0.000; ß-coefficient = 0.004; 95% confidence interval = -0.1542 to 0.1623). Transfused volume was not related to 30-day mortality (difference -0.162; -0.048 to 0.371 mL/kg; P = 0.112) or to postoperative ventilator support (R = 0.047), but was greater in patients who required reoperation (difference -0.246; -0.494 to -0.025; P = 0.004). Multiple regression analysis for all patients revealed age, preoperative ventilator support, prolonged postoperative ventilatory or vasoactive support, transplant year, and 30-day mortality, but not major adverse events, to be significant confounding variables. Adjusting for these variables, transfused volume was not associated with prolonged postoperative LOS. CONCLUSIONS: In contrast to a prior report, we found no correlation between intraoperative RBC transfusion and postoperative LOS when studying only infants. Infants have maturing organ systems, less physiologic reserve, and increased surgical blood loss (evaluated as mL/kg) during cardiac surgery than their larger, older counterparts, distinguishing them from the general pediatric population. These differences require additional studies to determine the outcome impact of transfusion strategies in the infant subgroup.

Advanced Monitoring Is Associated with Fewer Alarm Events During Planned Moderate Procedure-Related Sedation: A 2-Part Pilot Trial.

BACKGROUND: Diagnostic and interventional procedures are often facilitated by moderate procedure-related sedation. Many studies support the overall safety of this sedation; however, adverse cardiovascular and respiratory events are reported in up to 70% of these procedures, more frequently in very young, very old, or sicker patients. Monitoring with pulse oximetry may underreport hypoventilation during sedation, particularly if supplemental oxygen is provided. Capnometry may result in false alarms during sedation when patients mouth breathe or displace sampling devices. Advanced monitor use during sedation may allow event detection before complications develop. This 2-part pilot study used advanced monitors during planned moderate sedation to (1) determine incidences of desaturation, low respiratory rate, and deeper than intended sedation alarm events; and (2) determine whether advanced monitor use is associated with fewer alarm events. METHODS: Adult patients undergoing scheduled gastroenterology or interventional radiology procedures with planned moderate sedation given by dedicated sedation nurses under the direction of procedural physicians (procedural sedation team) were monitored per standard protocols (electrocardiography blood pressure, pulse oximetry, and capnometry) and advanced monitors (acoustic respiratory monitoring and processed electroencephalograpy). Data were collected to computers for analysis. Advanced monitor parameters were not visible to teams in part 1 (standard) but were visible to teams in part 2 (advanced). Alarm events were defined as desaturation-SpO2 ≤92%; respiratory depression, acoustic respiratory rate ≤8 breaths per minute, and deeper than intended sedation, indicated by processed electroencephalograpy. The number of alarm events was compared. RESULTS: Of 100 patients enrolled, 10 were excluded for data collection computer malfunction or consent withdrawal. Data were analyzed from 90 patients (44 standard and 46 advanced). Advanced had fewer total alarms than standard (Wilcoxon-Mann-Whitney = 2.073, P = 0.038; Wilcoxon-Mann-Whitney odds, 1.67; 95% confidence interval [CI], 1.04-2.88). Similar numbers of standard and advanced had ≥1 alarm event (Wald difference, -10.2%; 95% CI, -26.4% to 7.0%; P = 0.237). Fewer advanced patients had ≥1 respiratory depression event (Wald difference, -22.1%; 95% CI, -40.9% to -2.4%; P = 0.036) or ≥1 desaturation event (Wald difference, -24.2%; 95% CI, -42.8% to -3.6%; P = 0.021); but there was no significant difference in deeper than intended sedation events (Wald difference, -1.38%; 95% CI, -20.21% to 17.49%; P = 0.887). CONCLUSIONS: Use of advanced monitoring parameters during planned moderate sedation was associated with fewer alarm events, patients experiencing desaturation, and patients experiencing respiratory depression alarm events. This pilot study suggests that further study into the safety and outcome impacts of advanced monitoring during procedure-related sedation is warranted.

Thrombin Preconditioning in Surgical Brain Injury in Rats.

The surgical brain injury model replicates neurosurgical brain parenchymal damage. Postsurgical brain edema correlates with postoperative neurological dysfunction. Intranasal administration is a proven method of delivering therapies to brain tissue. Thrombin preconditioning decreased brain edema and improved neurological outcomes in models of ischemic brain injury. We hypothesized thrombin preconditioning in surgical brain injury may improve postoperative brain edema and neurological outcomes. Adult male Sprague-Dawley rats (n = 78) weighing 285-355 g were randomly assigned to sham or pre-injury treatment: one-time pretreatment 1 day prior, one-time pretreatment 5 days prior, and daily preconditioning for 5 days prior. Treatment arms were divided into vehicle or thrombin therapies, and subdivided into intranasal (thrombin 5 units/50 µL 0.9 % saline) or intracerebral ventricular (thrombin 0.1 unit/10 µL 0.9 % saline) administration. Blinded observers performed neurological testing 24 h after brain injury followed immediately by measurement of brain water content. There was a significant difference in ipsilateral brain water content and neurological outcomes between all treatment groups and the sham group. However, there was no change in brain water content or neurological outcomes between thrombin- and vehicle-treated animals. Thrombin preconditioning did not significantly improve brain edema or neurological function in surgical brain injury in rats.

Epsilon Aminocaproic Acid Pretreatment Provides Neuroprotection Following Surgically Induced Brain Injury in a Rat Model.

Neurosurgical procedures can damage viable brain tissue unintentionally by a wide range of mechanisms. This surgically induced brain injury (SBI) can be a result of direct incision, electrocauterization, or tissue retraction. Plasmin, a serine protease that dissolves fibrin blood clots, has been shown to enhance cerebral edema and hemorrhage accumulation in the brain through disruption of the blood brain barrier. Epsilon aminocaproic acid (EAA), a recognized antifibrinolytic lysine analogue, can reduce the levels of active plasmin and, in doing so, potentially can preserve the neurovascular unit of the brain. We investigated the role of EAA as a pretreatment neuroprotective modality in a SBI rat model, hypothesizing that EAA therapy would protect brain tissue integrity, translating into preserved neurobehavioral function. Male Sprague-Dawley rats were randomly assigned to one of four groups: sham (n = 7), SBI (n = 7), SBI with low-dose EAA, 150 mg/kg (n = 7), and SBI with high-dose EAA, 450 mg/kg (n = 7). SBI was induced by partial right frontal lobe resection through a frontal craniotomy. Postoperative assessment at 24 h included neurobehavioral testing and measurement of brain water content. Results at 24 h showed both low- and high-dose EAA reduced brain water content and improved neurobehavioral function compared with the SBI groups. This suggests that EAA may be a useful pretherapeutic modality for SBI. Further studies are needed to clarify optimal therapeutic dosing and to identify mechanisms of neuroprotection in rat SBI models.