A systematic review of outcomes reported inpediatric perioperative research: A report from the Pediatric Perioperative Outcomes Group.

The Pediatric Perioperative Outcomes Group (PPOG) is an international collaborative of clinical investigators and clinicians within the subspecialty of pediatric anesthesiology and perioperative care which aims to use COMET (Core Outcomes Measures in Effectiveness Trials) methodology to develop core outcome setsfor infants, children and young people that are tailored to the priorities of the pediatric surgical population.Focusing on four age-dependent patient subpopulations determined a priori for core outcome set development: i) neonates and former preterm infants (up to 60 weeks postmenstrual age); ii) infants (>60 weeks postmenstrual age - <1 year); iii) toddlers and school age children (>1-<13 years); and iv) adolescents (>13-<18 years), we conducted a systematic review of outcomes reported in perioperative studies that include participants within age-dependent pediatric subpopulations. Our review of pediatric perioperative controlled trials published from 2008 to 2018 identified 724 articles reporting 3192 outcome measures. The proportion of published trials and the most frequently reported outcomes varied across pre-determined age groups. Outcomes related to patient comfort, particularly pain and analgesic requirement, were the most frequent domain for infants, children and adolescents. Clinical indicators, particularly cardiorespiratory or medication-related adverse events, were the most common outcomes for neonates and infants < 60 weeks and were the second most frequent domain at all other ages. Neonates and infants <60 weeks of age were significantly under-represented in perioperative trials. Patient-centered outcomes, heath care utilization, and bleeding/transfusion related outcomes were less often reported. In most studies, outcomes were measured in the immediate perioperative period, with the duration often restricted to the post-anesthesia care unit or the first 24 postoperative hours. The outcomes identified with this systematic review will be combined with patient centered outcomes identified through a subsequent stakeholder engagement study to arrive at a core outcome set for each age-specific group.

Copper Speciation in Variably Toxic Sediments at the Ely Copper Mine, Vermont, United States.

At the Ely Copper Mine Superfund site, Cu concentrations exceed background values in both streamwater (160-1200 times) and sediments (15-79 times). Previously, these sediment samples were incubated with laboratory test organisms, and they exhibited variable toxicity for different stream sites. In this study we combined bulk- and microscale techniques to determine Cu speciation and distribution in these contaminated sediments on the basis of evidence from previous work that Cu was the most important stressor in this environment and that variable observed toxicity could have resulted from differences in Cu speciation. Copper speciation results were similar at microscopic and bulk scales. The major Cu species in the more toxic samples were sorbed or coprecipitated with secondary Mn (birnessite) and Fe minerals (jarosite and goethite), which together accounted for nearly 80% of the total Cu. The major Cu species in the less toxic samples were Cu sulfides (chalcopyrite and a covellite-like phase), making up about 80-95% of the total Cu, with minor amounts of Cu associated with jarosite or goethite. These Cu speciation results are consistent with the toxicity results, considering that Cu sorbed or coprecipitated with secondary phases at near-neutral pH is relatively less stable than Cu bound to sulfide at lower pH. The more toxic stream sediment sites were those that contained fewer detrital sulfides and were upstream of the major mine waste pile, suggesting that removal and consolidation of sulfide-bearing waste piles on site may not eliminate all sources of bioaccessible Cu.

Effects of Hypothermic Cardiopulmonary Bypass on Internal Jugular Bulb Venous Oxygen Saturation, Cerebral Oxygen Saturation, and Bispectral Index in Pediatric Patients Undergoing Cardiac Surgery: A Prospective Study.

The objective of this study was to evaluate the effect of hypothermic cardiopulmonary bypass (CPB) on cerebral oxygen saturation (rSO2), internal jugular bulb venous oxygen saturation (SjvO2), mixed venous oxygen saturation (SvO2), and bispectral index (BIS) used to monitor cerebral oxygen balance in pediatric patients.Sixty American Society of Anesthesiologists Class II-III patients aged 1 to 4 years old with congenital heart disease scheduled for elective cardiac surgery were included in this study. Temperature, BIS, rSO2, mean arterial pressure, central venous pressure, cerebral perfusion pressure (CPP), and hematocrit were recorded. Internal jugular bulb venous oxygen saturation and SvO2 were obtained from blood gas analysis at the time points: after induction of anesthesia (T0), beginning of CPB (T1), ascending aortic occlusion (T2), 20 minutes after initiating CPB (T3), coronary reperfusion (T4), separation from CPB (T5), and at the end of operation (T6). The effect of hypothermia or changes in CPP on rSO2, SjvO2, SvO2, and BIS were analyzed.Compared with postinduction baseline values, rSO2 significantly decreased at all-time points: onset of extracorporeal circulation, ascending aortic occlusion, 20 minutes after CPB initiation, coronary reperfusion, and separation from CPB (P < 0.05). Compared with measurements made following induction of anesthesia, SjvO2 significantly increased with initiation of CPB, ascending aortic occlusion, 20 minutes after initiating CPB, coronary reperfusion, and separation from CPB (P < 0.05). Compared with induction of anesthesia, BIS significantly decreased with the onset of CPB, aortic cross clamping, 20 minutes after initiating CPB, and coronary reperfusion (P < 0.05). Bispectral index increased following separation from CPB. There was no significant change in SvO2 during cardiopulmonary bypass (P > 0.05). Correlation analysis demonstrated that rSO2 was positively related to CPP (r = 0.687, P = 0.000), with a low linear correlation to temperature (r = 0.453, P = 0.000). Internal jugular bulb venous oxygen saturation was negatively related to temperature (r = -0.689, P = 0.000). Bispectral index was positively related to both temperature (r = 0.824, P = 0.000) and CPP (r = 0.782, P = 0.000). Cerebral oxygen saturation had a positive linear correlation with CPP and a low linear correlation to temperature. Internal jugular bulb venous oxygen saturation had a negative linear correlation to temperature.Pre-and and early postbypass periods are vulnerable times for adequate cerebral oxygenation. Anesthetic management must aim to optimize the supply and demand relationship.

Effects of sevoflurane on the expression of tau protein mRNA and Ser396/404 site in the hippocampus of developing rat brain.

BACKGROUND: General anesthesia induces a transient hyperphosphorylation of tau protein that is associated with neurotoxicity in neonatal rats, but the mechanism remains unknown. The current study sought to investigate the effects of sevoflurane on the levels of tau phosphorylation at phosphor-Ser396/404 and total tau mRNA in the hippocampus of neonatal rats. MATERIALS AND METHODS: Thirty-six 7-day-old rats were randomly exposed for 6 h to either 3% sevoflurane (S) or air (NC) as a placebo. They were sacrificed at 1, 7 and 14 days after the anesthesia, respectively, and thus assigned to S1d , S7d , S14d , NC1d , NC7d , and NC14d groups (n = 6). Their brain tissues were harvested and then subjected to histopathologic, Western blot and real-time polymerase chain reaction analysis. RESULTS: Microtubule cytoskeletons were arranged in neat parallel rows in rats exposed only to air, whereas the microtubules were arranged in a disorderly and intermittent (nonparallel) fashion in rats exposed to sevoflurane. The levels of tau mRNA in the S1d and S7d groups were significantly higher than those in the NC1d and NC7d groups. There was no significant difference in the levels of tau mRNA between the S14d and NC14d groups. The levels of tau protein at Ser404 in the S1d , S7d, and S14d groups were significantly higher than those in NC1d , NC7d, and NC14d groups. The levels of tau protein at Ser396 in the S1d , and S7d groups were significantly higher than those in the NC1d , and NC7d groups, while there was no significant difference in the levels of tau protein at Ser396 between the S14d group and the NC14d group, respectively. CONCLUSION: In rat hippocampus, sevoflurane was associated with microtubular disarray as well as increased levels of tau mRNA and excessive phosphorylation of tau protein at Ser396 and Ser404. This implicates that sevoflurane may induce neurotoxicity.

Randomized trial of success of pediatric anesthesiologists learning to use two video laryngoscopes.

OBJECTIVES: The primary purpose of this study was to establish the ability of pediatric anesthesiologists to learn to use two video laryngoscopes - the GlideScope(®) system (GS) and the Karl Storz Direct Coupled Interface, DCI(®), (KS). BACKGROUND: The number of intubation attempts required to attain proficiency with a video laryngoscope is not known. METHODS: Baseline intubation times, using direct laryngoscopy, were determined for each anesthesiologist on 20 children. Anesthesiologists were then randomized to perform 20 intubations with the GS or KS before crossing over to the other device. RESULTS: There were 193 successful intubations and eight failed intubations (4.0%) with the GS. Median time-to-intubation with the GS for each anesthesiologist ranged from 24.5 to 32.8 s. There were 193 successful intubations and three failed intubations (1.5%) with the KS (P > 0.05 vs failed attempts with GS). Median time-to-intubation with the KS ranged from 21.9 to 31.1 s. For both the GS and KS, five of eight anesthesiologists met the study definition of 'Success'. There was no correlation between median time-to-intubation with all laryngoscopes combined and years since completion of training. The distribution of Cormack and Lehane scores was almost identical for the GS and KS; there were fewer grade III or IV scores than with direct laryngoscopy (P = 0.03; Fischer's exact test). Mean and median times on intubation no. 16-20 were shorter for the KS than for the GS. CONCLUSIONS: Although only 65% of anesthesiologists attained the stringent study definition of 'Success', all rapidly leaned to use both video laryngoscopes.

Adult congenital heart disease.

For a decade now, it has been recognized that optimal management of adult congenital heart disease (ACHD) requires a skilled multidisciplinary team. The size and complexity of the population of adults with congenital heart disease (CHD) are increasing. This article reviews the general considerations for giving an anesthetic to an adult with CHD for cardiac or noncardiac surgery and provides further elaboration for a variety of complex patient types. Lastly, the advantages of an organized multidisciplinary approach to patients with ACHD are discussed.

Comparison of bupivacaine and 2-chloroprocaine for spinal anesthesia for outpatient surgery: a double-blind randomized trial.

BACKGROUND: We have always been searching for the ideal local anesthetic for outpatient spinal anesthesia. Lidocaine has been associated with a high incidence of transient neurological symptoms, and bupivacaine produces sensory and motor blocks of long duration. Preservative-free 2-chloroprocaine (2-CP) seems to be a promising alternative, being a short-acting agent of increasing popularity in recent years. This study was designed to compare 2-CP with bupivacaine for spinal anesthesia in an elective ambulatory setting. METHODS: A total of 106 patients were enrolled in this randomized double-blind study. Spinal anesthesia was achieved with 0.75% hyperbaric bupivacaine 7.5 mg (n = 53) or 2% preservative-free 2-CP 40 mg (n = 53). The primary endpoint for the study was the time until reaching eligibility for discharge. Secondary outcomes included the duration of the sensory and motor blocks, the length of stay in the postanesthesia care unit, the time until ambulation, and the time until micturition. RESULTS: The average time to discharge readiness was 277 min in the 2-CP group and 353 min in the bupivacaine group, a difference of 76 min (95% confidence interval [CI]: 40 to 112 min; P < 0.001). The average time for complete regression of the sensory block was 146 min in the 2-CP group and 329 min in the bupivacaine group, a difference of 185 min (95% CI: 159 to 212 min; P < 0.001). Times to ambulation and micturition were also significantly lower in the 2-CP group. CONCLUSION: Spinal 2-chloroprocaine provides adequate duration and depth of surgical anesthesia for short procedures with the advantages of faster block resolution and earlier hospital discharge compared with spinal bupivacaine. (ClinicalTrials.gov number, NCT00845962).

Evaluation of the addition of bupivacaine to intrathecal morphine and fentanyl for postoperative pain management in laparascopic liver resection.

BACKGROUND: Optimal modality of pain management after liver resection has been controversial. Epidural analgesia is often avoided because of transient coagulopathy and the associated risk of epidural hematoma. Single-dose intrathecal morphine has been shown to be an effective alternative in open liver resection. The purpose of this trial was to compare the analgesic efficacy of intrathecal morphine and fentanyl versus intrathecal bupivacaine 0.5%, morphine, and fentanyl for patients undergoing laparoscopic liver resection. METHODS: This prospective randomized controlled double-blind trial compared morphine consumption between control (CTRL) group receiving a spinal injection of fentanyl 15 µg and morphine 0.4 mg and bupivacaine (BUPI) group receiving the same medications in addition to bupivacaine 0.5% (15 mg). Forty patients scheduled for laparoscopic liver resection were enrolled. Primary outcome was intravenous patient-controlled analgesia morphine consumption measured at 6, 9, 12, 18, 24, 36, and 48 hrs after spinal injection. Secondary outcomes were pain scores at rest and with movement, sedation, nausea, pruritus, and respiratory rate. RESULTS: Cumulative doses of morphine were significantly lower for all time intervals in the BUPI group: 54 (30) versus 94 (47) mg (P = 0.01) at 48 hrs. Morphine consumption was significantly lower for each time interval up to 18 hrs. Pain scores with movement were significantly lower in the BUPI group up to 24 hrs after injection. Pain score at rest was significantly lower in the BUPI group 9 hrs after injection. There were no differences in adverse effects. CONCLUSIONS: The addition of bupivacaine to intrathecal morphine and fentanyl significantly reduced intravenous morphine consumption after laparoscopic liver resection.

Swine influenza (H3N2) infection in a child and possible community transmission, Canada.

An influenza A virus (H3N2) of probable swine origin, designated A/Canada/1158/2006, was isolated from a 7-month-old hospitalized child who lived on a communal farm in Canada. The child recovered uneventfully. A serosurvey that used a hemagglutination-inhibition assay for A/Canada/1158/2006 was conducted on 54 of the 90 members of the farm. Seropositivity was demonstrated in the index patient, 4 of 7 household members, and 4 of 46 nonhousehold members; none had a history of hospital admission for respiratory illness in the preceding year. Serologic evidence for this strain of swine influenza was also found in 1 of 10 pigs (12 weeks-6 months of age) on the farm. Human infection with swine influenza virus is underrecognized in Canada, and because viral strains could adapt or reassort into a form that results in efficient human-to-human transmission, routine surveillance of swine workers should be considered as part of pandemic influenza preparedness.

A comparison of intrathecal morphine/fentanyl and patient-controlled analgesia with patient-controlled analgesia alone for analgesia after liver resection.

Continuous epidural anesthesia and analgesia may be considered in liver resection, but is often avoided because of the potential development of coagulopathies and the risk of epidural hematoma. In this prospective, randomized, double-blind study we compared postoperative morphine consumption via patient-controlled analgesia after liver surgery between two groups of patients: patients receiving a preoperative dose of intrathecal morphine (0.5 mg) and fentanyl (15 microg) (treatment group) and patients receiving a sham intrathecal injection (placebo group). Forty patients scheduled for major liver resection (> or = two segments) were enrolled. The primary outcome measure was patient-controlled analgesia morphine consumption. Secondary outcomes were evaluation of pain at rest and with movement, scored on a visual analog scale with assessment of sedation, nausea, pruritus, and respiratory frequency. Outcome measures were recorded at 6, 12, 18, 24, and 48 h postspinal anesthesia or simulation. Patients in the placebo group consumed approximately three times more morphine during each time interval than patients in the treatment group (at 48 h: 124 +/- 30 vs 47 +/- 21 mg, P < 0.0001). Pain evaluation on the visual analog scale was lower for the first 18 h in the treatment group. There was no difference in the incidence of side effects in both groups. Intrathecal morphine (0.5 mg) and fentanyl (15 microg) given before liver surgery significantly decreased postoperative morphine consumption compared to placebo without any increase in side effects.

Effect of low central venous pressure and phlebotomy on blood product transfusion requirements during liver transplantations.

Correction of coagulation defects with plasma transfusion did not decrease the need for intraoperative red blood cells (RBC) transfusions during liver transplantations. On the contrary, it led to a hypervolemic state that resulted in an increase of shed blood. As well, plasma transfusion has been associated with a decreased one-year survival rate. The aim of the present prospective survey was to evaluate whether anesthesiologists could reduce intraoperative RBC transfusions during liver transplantations by changing their anesthesia practice, more specifically by maintaining a low central venous pressure (CVP), through restriction of volume replacement, elimination of all plasma transfusion and by using intraoperative phlebotomy during the transplantation. One hundred consecutive liver transplantations were prospectively studied during a two-year period and were compared to a retrospective series (1998-2002). A low CVP was maintained in all patients prior the anhepatic phase. Coagulation disorders were not corrected preoperatively, intraoperatively, or post-operatively unless uncontrollable bleeding. Phlebotomy and Cell Saver (CS) were used following pre-established criteria. Independent variables were analyzed in a univariate and multivariate fashion. The mean number of intraoperative RBC units transfused was 0.4 +/- 0.8. No plasma, platelets, albumin, or cryoprecipitate were transfused. Seventy-nine percent of the patients received no blood products during their liver transplantation. The average final hemoglobin value was 85.9 +/- 17.8 g/L. In 57 patients (58.2%), intraoperative phlebotomy and CS were used either together or separately. The one-year year survival rate was 89.1%. Logistic regression showed that avoidance of plasma transfusion, starting hemoglobin value and phlebotomy were significantly linked to liver transplantation without RBC transfusion. In conclusion, the avoidance of plasma transfusion and maintenance of a low CVP prior to the anhepatic phase were associated with a decrease in RBC transfusions during liver transplantations. Previous reports indicating that it is neither useful nor necessary to correct coagulation defects with plasma transfusion prior to liver transplantation are further corroborated by this prospective survey. We believe that this work also supports the practice of lowering CVP with phlebotomy in order to reduce blood loss, during liver dissection, without any deleterious effect.

Can continuous low current electrical stimulation distinguish insulated needle position in the epidural and intrathecal spaces in pediatric patients?

BACKGROUND: Muscle twitches elicited with electrical stimulation (6-17 mA) during epidural insertion indicate correct epidural needle placement while muscle twitches at a lower current (<1 mA) may indicate intrathecal needle placement. This study examined whether applying continuous electrical stimulation at 6 mA could indicate needle entry into the epidural space without inadvertently penetrating the intrathecal space. METHODS: After institutional review board (IRB) approval, 10 pediatric patients scheduled for lumbar puncture were studied. Following sedation with propofol, an insulated 24-gauge Pajunck unipolar needle was inserted through an 18-gauge introducer needle placed at the L4-5 interspace. The needle was first connected to a nerve stimulator (6 mA) and advanced. At the first sign of muscle twitching, needle advancement was stopped and the threshold current for motor activity was determined. The current was then turned off, the stylet was removed and the needle checked for cerebrospinal fluid (CSF). If CSF was not present, the needle was advanced into the intrathecal space (as confirmed by the presence of CSF). Ten pediatric patients (ASA II or III) aged 7.8 +/- 4.3 years (2.8-16.0 years) were studied. RESULTS: All patients had two distinguishable threshold currents as the needle advanced. The mean threshold current to elicit muscle twitch in the presumed epidural space was 3.84 +/- 0.99 mA. CSF was not present in any of the patients at this location. The mean threshold current in the intrathecal space was 0.77 +/- 0.32 mA. The average estimated distance from the first threshold location to the intrathecal space was 3 mm. All muscle twitches were at the L3-5 myotomes. Nine muscle twitches were unilateral and one was bilateral. CONCLUSIONS: Monitoring with an insulated needle with electrical stimulation at 6 mA may prevent unintentional placement of epidural needles into the intrathecal space.

Survival rate changes with transfusion of blood products during liver transplantation.

PURPOSE: To determine whether red blood cell (RBC) or plasma transfusion is associated with the one-year survival rate variation previously detected in liver transplantation. METHODS: A retrospective study of 206 consecutive liver transplantations was undertaken. Intraoperative transfusions of blood products were identified. Twenty-seven variables were studied using univariate and multivariate analyses to identify factors that were associated significantly with survival rate. For analysis of one-year survival, the cases were studied according to the transfused blood products. Patients were stratified according to the degree of RBC and plasma transfusion into four groups: more than four units of RBC, one to four units of RBC, plasma transfusion only, and no plasma or RBC transfusions. RESULTS: Patients received an average of 2.8 +/- 3.5 units of RBC and 4.1 +/- 4.1 units of plasma. Thirty-two percent of the patients did not receive any RBC transfusion and 19.4% did not receive any blood products. The one-year survival rate was 81.9% for all patients and 97.4% for patients without any transfusions. Of the 27 variables evaluated, only RBC and plasma transfusions were associated with significant decrease in the one-year survival rate, which was seen in the group who received only plasma (76.9%, P = 0.014) and the group who received more than four units of RBC (62.5%, P < 0.0001). CONCLUSION: Although we cannot demonstrate causality, our analysis shows that our one-year survival rate following liver transplantation decreased significantly with the intraoperative transfusion of any amount of plasma or more than four units of RBC.

Threshold current of an insulated needle in the intrathecal space in pediatric patients.

A threshold current of <1 mA has been suggested to be sufficient to produce a motor response to electrical stimulation in the intrathecal space. We designed this study to determine the threshold current needed to elicit motor activity for an insulated needle in the intrathecal space. Twenty pediatric patients aged 7.3 +/- 3.9 yr scheduled for lumbar puncture were recruited. After sedation with propofol, patients were turned to the lateral position and an 18-gauge or 20-gauge introducer needle was placed at the L4-5 level through which an insulated 24-gauge Pajunck unipolar needle (with a Sprotte tip and stylet) was inserted. The needle was advanced into the intrathecal space as suggested by the presence of a "pop." At this point, a nerve stimulator was attached to the insulated needle and the current was gradually increased until motor activity was evident. The needle hub was checked for cerebrospinal fluid. If cerebrospinal fluid was not present, the needle was advanced further until cerebrospinal fluid was present. The threshold current was retested. The mean current in the intrathecal space required to elicit a motor response was 0.6 +/- 0.3 mA (range, 0.1-1 mA). In 19 patients, the twitches were observed at the L4-5 myotomes and 1 patient had twitches at L2. Twitches were observed unilaterally in 19 children and bilaterally in one child. This confirms the hypothesis that the threshold current in the intrathecal space is <1 mA and that it differs significantly from the threshold currents reported for electrical stimulation in the epidural space.

Determination of epsomite-hexahydrite equilibria by the humidity-buffer technique at 0.1 MPa with implications for phase equilibria in the system MgSO4-H2O.

Epsomite (MgSO(4).7H(2)O) and hexahydrite (MgSO(4).6H(2)O) are common minerals found in marine evaporite deposits, in saline lakes as precipitates, in weathering zones of coal and metallic deposits, in some soils and their efflorescences, and possibly on the surface of Europa as evaporite deposits. Thermodynamic properties of these two minerals reported in the literature are in poor agreement. In this study, epsomite-hexahydrite equilibria were determined along four humidity-buffer curves at 0.1 MPa and between 25 and 45 degrees C. Results obtained for the reaction epsomite = hexahydrite + H(2)O, as demonstrated by very tight reversals along each humidity buffer, can be represented by ln K(+/- 0.012) = 20.001 - 7182.07/T, where K is the equilibrium constant, and T is temperature in Kelvin. The derived standard Gibbs free energy of reaction is 10.13 +/- 0.07 kJ/mol, which is essentially the same value as that calculated from vapor pressure measurements reported in the literature. However, this value is at least 0.8 kJ/mol lower than those calculated from the data derived mostly from calorimetric measurements.