Clinical impact of term-equivalent magnetic resonance imaging in extremely low-birth-weight infants at a regional NICU.

OBJECTIVE: To evaluate the clinical impact of routine term-equivalent magnetic resonance imaging (TE-MRI) for extremely low-birth-weight infants at a regional neonatal intensive care unit. STUDY DESIGN: This is a single-center retrospective study evaluating preterm survivors who underwent TE-MRI. MRI abnormalities were compared between infants with and without cranial ultrasonography (CUS) abnormalities. Cost analysis comparing imaging modalities was also performed. RESULTS: TE-MRI use increased from 17% in 2006 to 76% in 2010. MRI detected new findings in nearly half of infants, whether or not they had known ultrasound abnormalities. MRI detected more cerebellar (18% vs 6%, P=0.04) and moderate white matter injury (12% vs 7%, P<0.001), and altered simulated neurological prognosis across developmental domains. The cost of TE-MRI was $1600, which was comparable to serial CUSs. CONCLUSION: TE-MRI detects new abnormalities and impacts developmental prognosis in the extremely low birth weight, which supports its use despite the added financial cost.

Resuscitation fluid use in Australian and New Zealand Intensive Care Units between 2007 and 2013.

INTRODUCTION: Recent evidence indicates that the choice of intravenous fluids may affect outcomes in critically ill patients. METHODS: We recorded the administration of resuscitation fluids in patients admitted to Australian and New Zealand adult intensive care units (ICUs) for a 24-h period at 6 time points between 2007 and 2013. Changes in patterns of fluid use over this period were determined using regression analyses. RESULTS: Of the 2825 patients admitted to the 61 ICUs on the 6 study days, 754 (26.7%) patients received fluid resuscitation. Of those receiving fluid resuscitation, the proportion of patients receiving crystalloid significantly increased from 28.9% (41/142) in 2007 to 50.5% (48/95) in 2013 (adjusted odds ratio (OR) 2.93; 95% confidence intervals (CI) 1.35-6.33; p = 0.006); of these, the proportion of patients receiving buffered salt solutions significantly increased from 4.9% (7/142) in 2007 to 31.6% (30/95) in 2013 (OR 7.00; 95% CI 2.14-22.92; p = 0.001). The use of colloids significantly decreased from 59.9% (85/142) in 2007 to 42.1% (40/95) in 2013 (adjusted OR 0.34; 95% CI 0.16-0.74; p = 0.007) due to a significant decrease in the proportion of patients receiving gelatin; 28.9% (41/142) to 2.1% (2/95) (OR 0.10; 95% CI 0.03-0.29; p ≤ 0.001). CONCLUSION: Fluid resuscitation practice in Australia and New Zealand adult ICUs has changed over the 6-year study period. Crystalloid use increased primarily due to an increase in the use of buffered salt solutions while overall the use of colloid has decreased.

Heart rate variability in encephalopathic newborns during and after therapeutic hypothermia.

OBJECTIVE: To evaluate whether heart rate variability (HRV) measures are predictive of neurological outcome in babies with hypoxic ischemic encephalopathy (HIE). STUDY DESIGN: This case-control investigation included 20 term encephalopathic newborns treated with systemic hypothermia in a regional neonatal intensive care unit. Electrocardiographic data were collected continuously during hypothermia. Spectral analysis of beat-to-beat heart rate interval was used to quantify HRV. HRV measures were compared between infants with adverse outcome (death or neurodevelopmental impairment at 15 months, n = 10) and those with favorable outcome (survivors without impairment, n = 10). RESULT: HRV differentiated infants by outcome during hypothermia through post-rewarming, with the best distinction between groups at 24 h and after 80 h of life. CONCLUSION: HRV during hypothermia treatment distinguished HIE babies who subsequently died or had neurodevelopmental impairment from intact survivors. This physiological biomarker may identify infants in need of adjuvant neuroprotective interventions. These findings warrant further investigation in a larger population of infants with HIE.

Neurobehavioral assessment as a predictor of neurodevelopmental outcome in preterm infants.

OBJECTIVE: Preterm infants are at risk for neurodevelopmental impairment. The Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) is a standardized assessment for the neurobehavioral integrity of the newborn. The use of NNNS as a prognostic tool is still emerging. We hypothesized that the NNNS examination performed at term equivalent can detect neurobehavioral alterations in very low birth weight infants and can help in predicting their neurodevelopmental outcome at 18 months corrected age (CA). STUDY DESIGN: This is a prospective study that included preterm infants with birth weight <1500 g and gestational age ≤ 34 weeks. They were evaluated with NNNS at term-equivalent and 12 summary scores were assigned. Infants who had 2 or more NNNS summary scores that were 2 s.d. beyond the mean of the study group were categorized as having abnormal NNNS. Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of Bayley Scales of Infant Development (BSID-II) were determined at 18 months CA. Multiple linear regression models were used to examine the predictivity of the NNNS summary scores for both MDI and PDI. RESULT: A total of 41 infants were evaluated at term and at 18 months CA. The average MDI was 78±15 and the average PDI was 80 ± 14. Significant neurodevelopmental delay was observed in 50% and 31% of infants with abnormal and normal NNNS, respectively. Using multiple linear regression, NNNS was predictive for both MDI (P=0.011, adjusted R (2)=0.295) and PDI (P=0.002, adjusted R (2)=0.441). Lower MDI was associated with less regulation and more nonoptimal reflexes, whereas lower PDI was associated with less regulation, more nonoptimal reflexes, hypertonicity and handling. CONCLUSION: NNNS at term-equivalent age can detect neurobehavioral alterations in very low birth weight infants. Individual summary scores showed significant correlation with both the MDI and PDI at 18 months CA.

Multimodal therapies for postoperative nausea and vomiting, and pain.

Postoperative nausea and vomiting (PONV) and pain are two of the major concerns for patients presenting for surgery. The causes of PONV are multifactorial and can largely be categorized as patient risk factors, anaesthetic technique, and surgical procedure. Antiemetics work on several different receptor sites to prevent or treat PONV. This is probably why numerous studies have now demonstrated that using more than one antiemetic is usually more effective and results in fewer side-effects than simply increasing the dose of a single antiemetic. A multimodal approach to PONV should not be limited to drug therapy alone but should involve a holistic approach starting before operation and continuing intraoperatively with risk reduction strategies to which are added prophylactic antiemetics according to the assessed patient risk for PONV. With the increasing understanding of the pathophysiology of acute pain, especially the occurrence of peripheral and central hypersensitization, it is unlikely that a single drug or intervention is sufficiently broad in its action to be adequately effective, especially with moderate or greater pain. Although morphine and its congeners are usually the foundation of pain management regimens, as their dose increases so does the incidence of side-effects. Thus, the approach for the management of acute postoperative pain is to use multiple drugs or modalities (e.g. regional anaesthesia) to maximize pain relief and reduce side-effects.

Compliance with processes of care in intensive care units in Australia and New Zealand--a point prevalence study.

There are indications that compliance with routine clinical practices in intensive care units (ICU) varies widely internationally, but it is currently unknown whether this is the case throughout Australia and New Zealand. A one-day point prevalence study measured the prevalence of routine care processes being delivered in Australian and New Zealand ICUs including the assessment and/or management of: nutrition, pain, sedation, weaning from mechanical ventilation, head of bed elevation, deep venous thrombosis prophylaxis, stress ulcer prophylaxis, blood glucose, pressure areas and bowel action. Using a sample of 50 adult ICUs, prevalence data were collected for 662 patients with a median age of 65 years and a median Acute Physiology and Chronic Health Evaluation II score of 18. Wide variations in compliance were evident in several care components including: assessment of nutritional goals (74%, interquartile range [IQR] 51 to 89%), pain score (35%, IQR 17 to 62%), sedation score (89%, IQR 50 to 100%); care of ventilated patients e.g. head of bed elevation > 30 degrees (33%, IQR 7 to 62%) and setting weaning plans (50%, IQR 28 to 78%); pressure area risk assessment (78%, IQR 18 to 100%) and constipation management plan (43%, IQR 6 to 87%). Care components that were delivered more consistently included nutrition delivery (100%, IQR 100 to 100%), deep venous thrombosis (96%, IQR 89 to 100%) and stress ulcer (90%, IQR 78 to 100%) prophylaxis, and checking blood sugar levels (93%, IQR 88 to 100%). This point prevalence study demonstrated variability in the delivery of 'routine' cares in Australian and New Zealand ICUs. This may be driven in part by lack of consensus on what is best practice in intensive care units, prompting the need for further research in this area.

Age-associated differences in the inhibition of mitochondrial permeability transition pore opening by cyclosporine A.

BACKGROUND: Inhibiting mitochondrial permeability transition pore (mPTP) opening is a key protection of the myocardium from ischemia/reperfusion (I/R) injury. Here, we investigated age-associated differences in the ability of cyclosporine A (CsA) to protect the heart and to modulate mPTP opening during I/R injury in vivo and its opening induced by reactive oxygen species (ROS) in vitro. METHODS: Fischer 344 male rats were assigned from their respective age groups, young or old groups, to (1) I/R or (2) I/R+CsA. All animals were subjected to 30 min of ischemia following 120 min of reperfusion to determine myocardial infarct size in vivo. To measure mPTP opening in vivo, left ventricular tissues were collected 10 min after reperfusion and nicotinamide adenine dinucleotide (NAD(+)) levels were measured. In parallel experiments, rat ventricular myocytes were prepared from young and old hearts, loaded with tetramethylrhodamine ethylester and then subjected to oxidative stress in the presence or absence of CsA, and the mPTP opening time was measured using laser scanning confocal microscopy. RESULTS: CsA reduced myocardial infarct size in young I/R rats. Whereas CsA failed to significantly affect myocardial infarct size in old I/R rats, NAD(+) levels were better preserved in young CsA-treated rats, but this relative improvement was not observed in old rats. CsA also significantly prolonged the time necessary to induce mPTP opening in young cardiomyocytes, but not in cardiomyocytes isolated from the old rats. CONCLUSIONS: mPTP regulation is dysfunctional in the aged myocardium and this could account for loss of cardioprotection with aging.

Quantitative analysis of magnetic resonance images and neurological outcome in encephalopathic neonates treated with whole-body hypothermia.

OBJECTIVE: To evaluate whether quantitative measures from magnetic resonance imaging (MRI) performed in hypothermia-treated encephalopathic newborns can differentiate patients with unfavorable neurological outcome. STUDY DESIGN: Retrospective analysis of clinical data and MRI studies was performed in 47 full-term infants treated with whole-body hypothermia for neonatal encephalopathy. Apparent diffusion coefficients (ADCs) and T1 and T2 intensity ratios were measured in the basal ganglia and thalamus on axial MRI images. Unfavorable outcome was defined as (1) death or severe neurological deficits at discharge and (2) death or cerebral palsy/severe motor deficit at follow-up through age 9 months. Differences between groups with favorable versus unfavorable neurological outcome at each time point were compared. Optimal cutoff values for significant MR variables were determined with receiver operating curve analyses. Sensitivity and specificity of these cutoff values for predicting unfavorable outcome were calculated and results were compared with qualitative MRI interpretation. RESULT: Infants presented with a median pH of 6.86, base deficit of 20 and Apgar scores of 1, 3 and 4 at 1, 5 and 10 min, respectively. Severe encephalopathy was present in 38%. Unfavorable outcome was present in 9 patients at discharge and in 13 of 26 patients with available follow-up data through 9 months. ADC values and T1 ratios were not significantly different between groups at either time point. T2 ratios in both the basal ganglia and thalamus were significantly higher in patients with unfavorable outcome, both at discharge and in follow-up. T2 intensity ratio in the basal ganglia and thalamus remained significantly associated with death or severe neurological deficit at discharge, after controlling for covariates in logistic regression analysis. Sensitivity and specificity of T2 intensity ratio for predicting unfavorable outcome at discharge were comparable to qualitative grading of injury in the basal ganglia and thalamus by a neuroradiologist. CONCLUSION: Increased T2 signal intensity in the basal ganglia or thalamus in patients with hypothermia-treated neonatal encephalopathy is associated with unfavorable neurological outcome at discharge and later with motor deficit/cerebral palsy. Quantitative methods to assess MRI evidence of brain injury are important for providing objective measures to predict outcome in this high-risk population.

The effect of desflurane on rocuronium onset, clinical duration and maintenance requirements.

Volatile anesthetics potentiate the effects of non-depolarizing agents. This study investigated the interaction between the inhalational anesthetic desflurane and rocuronium. Forty ASA I and II patients randomly received desflurane/N2O/fentanyl, or propofol/ N2O/fentanyl anesthesia, and rocuronium 0.6 mg/kg. Neuromuscular block was assessed at the adductor pollicis muscle. Block onset and clinical duration times were measured; a rocuronium infusion was started when the first twitch on train-of-four returned to 10% of control (T10%). Maintenance infusion requirements and recovery profiles (spontaneous and after reversal) were recorded until recovery of twitch to 90% of control (T90%). Rocuronium onset was prolonged by 67% (p = 0.034), clinical duration by 30% (p = NS), and infusion requirements were lower in the desflurane group (4.5 vs. 7.1 mg/kg/min, p = 0.003). Recovery times were not statistically different. Desflurane significantly delays the onset of neuromuscular block, potentiates rocuronium during maintenance infusion, but does not affect clinical duration or recovery.

Does functional ability in the postoperative period differ between remifentanil- and fentanyl-based anesthesia?

STUDY OBJECTIVES: To compare patients' functional ability in the 24-hour postoperative period following a remifentanil compared to a hypnotic-fentanyl-treated anesthesia regimen using a 24-Hour Functional Ability Questionnaire. DESIGN: Prospective, 1:1 single-blind, randomized, controlled effectiveness study. SETTING: Multicenter study including 156 hospitals and ambulatory surgery facilities. PATIENTS: 2438 patients (1496 outpatients and 942 inpatients) 18 years of age or older, scheduled for elective surgeries under general endotracheal anesthesia, with an expected duration of unconsciousness of > or =30 minutes. INTERVENTIONS: Patients were randomized to receive either intravenous remifentanil (0.5 microg/kg/min for induction and intubation; with the infusion rate decreased to 0.25 microg/kg/min after intubation) or fentanyl (administered according to anesthesiologists' usual practice) as the opioid during surgery. Concomitant hypnotic drugs were propofol and/or isoflurane (with or without nitrous oxide) titrated according to protocol. Transition analgesia with either morphine or fentanyl was given in the remifentanil patients and at the discretion of the anesthesiologists in the fentanyl patients. MEASUREMENTS: A validated set of measurements of functional ability, rather than more traditional clinical psychological methods, to compare the recovery of patients from remifentanil- and fentanyl-treated anesthetic regimens up to 24 hours after surgery. MAIN RESULTS: Remifentanil was statistically superior to fentanyl for the four functional assessments evaluated: walking without dizziness, thinking clearly, concentration, and communicating effectively. These differences reflect events occurring within the first 24 hours after anesthesia and surgery. CONCLUSIONS: A remifentanil-treated anesthetic demonstrated earlier return to some functions than a fentanyl-treated technique. Although functional assessment is a field that is still in its infancy, a questionnaire to assess functional ability during the 24 hours after anesthesia may provide more practical information about anesthetic recovery than previously used, traditional psychomotor evaluations.

A case of tracheal injury after emergent endotracheal intubation: a review of the literature and causalities.

IMPLICATIONS: Tracheal lacerations are rare, but potentially fatal, complications of intubations. Diagnosis of such conditions is difficult, and thus a high level of suspicion must be kept. We present a case and review the literature for factors that indicate high-risk patients.

Duration of action of vecuronium after an intubating dose of rapacuronium, vecuronium, or succinylcholine.

UNLABELLED: Rapacuronium (RAP) is a new, rapid-onset, short-duration, nondepolarizing neuromuscular blocker. If RAP is used to facilitate endotracheal intubation, what will the duration of a subsequent maintenance dose of vecuronium (VEC) be? We investigated the duration of action of a maintenance dose of VEC after intubation with RAP, VEC, or succinylcholine (SUC). Adult surgical patients under general anesthesia were randomly allocated to receive a tracheal intubating dose of RAP 1.5 mg/kg, VEC 0.1 mg/kg, or SUC 1 mg/kg. The anesthetic was induced with propofol and maintained with propofol, nitrous oxide, and oxygen. Neuromuscular function was monitored with electromyography. Recovery of the intubating dose of neuromuscular blocker was allowed to occur spontaneously until the first twitch of the train-of-four (T1) reached 50% of baseline, and then VEC 0.025 mg/kg (0.5 x 95% effective dose [ED(95)]) was administered. The onset, duration, and recovery to T1 = 25% and 50% were recorded. The durations of action (recovery of T1 25%) after intubating doses of RAP, VEC, and SUC were 13.7 +/- 5.3, 43.2 +/- 13.2, and 9.2 +/- 3.7 min (mean +/- SD), respectively (P < 0.0001). The times to maximum depression of T1 after a maintenance dose of VEC (0.5 x ED(95)) were 5.4 +/- 2.9, 5.1 +/- 2.5, and 5.3 +/- 2.8 min (mean +/- SD) for the RAP, VEC, and SUC groups, respectively. Recoveries to T1 25% after VEC for the RAP, VEC, and SUC groups were 18.9 +/- 11.5, 21.5 +/- 8.03, and 12.8 +/- 8.4 min, and at T1 50% they were 21.5 +/- 9.1, 30.8 +/- 9.5, and 15.5 +/- 9.7 min (mean +/- SD), respectively (P < 0.001, RAP and VEC versus SUC). The duration of action of a maintenance dose of VEC was similar after an intubating dose of RAP or VEC but was shortened when preceded by an intubating dose of SUC. IMPLICATIONS: The duration of action of a maintenance dose of vecuronium was longer after an endotracheal intubating dose of rapacuronium compared with succinylcholine.

Assessment of depth of anesthesia and postoperative respiratory recovery after remifentanil- versus alfentanil-based total intravenous anesthesia in patients undergoing ear-nose-throat surgery.

BACKGROUND: The authors investigated whether total intravenous anesthesia (TIVA) with precalculated equipotent infusion schemes for remifentanil and alfentanil would ensure appropriate analgesia and that remifentanil would result in better recovery characteristics. METHODS: Forty consenting patients (classified as American Society of Anesthesiologists physical status I-III) scheduled for microlaryngoscopy were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 microg/kg; maintenance infusion, 0.25 microg x kg(-1) x min-1) or alfentanil (loading dose, 50 microg/kg; maintenance infusion, 1 microg x kg(-1) x min-1) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg/kg; maintenance infusion, 100 microg x kg(-1) min(-1)). To insure an equal state of anesthesia, the opioids were titrated to maintain heart rate and mean arterial pressure within 20% of baseline, and propofol was titrated to keep the bispectral index (BIS) less than 60. Neuromuscular blockade was achieved with succinylcholine. Drug dosages and the times from cessation of anesthesia to extubation, verbal response, recovery of ventilation, and neuropsychological testing, orientation, and discharge readiness were recorded. RESULTS: Demographics, duration of surgery, and anesthesia were similar between the two groups. Both groups received similar propofol doses. There were no difference in BIS values preoperatively (mean, 96), intraoperatively (mean, 55), and postoperatively (mean, 96). Recovery of BIS and times for verbal response did not differ. At 20, 30, and 40 min after terminating the opioid infusion, the peripheral oxygen saturation and respiratory rate were significantly higher in the remifentanil group compared with the alfentanil group. CONCLUSIONS: When both the hypnotic and analgesic components of a TIVA-based anesthetic are administered in equipotent doses, remifentanil provides a more rapid respiratory recovery, even after brief surgical procedures, compared with alfentanil.

Intravenous anesthetics.

Intravenous anesthetics continue to be a mainstay in the modern anesthesiologist's armamentarium. In this review the authors will discuss new advancements in the use of propofol, as well as a greater understanding as to its mechanism of action. Further, we will discuss the use of target controlled infusion systems, touch upon the possible benefits of the ultra-short acting opioids, and consider the role of alpha-2 agonists as an adjunct to anesthetic management.

Arm pain as an unusual presentation of postdural puncture intracranial hypotension.

IMPLICATIONS: We report a case of a patient experiencing severe arm pain after dural puncture. This complication has not been reported previously. The patient was successfully treated with an epidural patch.

The use of propofol for its antiemetic effect: a survey of clinical practice in the United States.

STUDY OBJECTIVES: To investigate the use of propofol by anesthesiologists for its antiemetic effect and to compare our findings with published evidence. DESIGN: Anonymous survey of U.S. anesthesiologists. SETTING: American Society of Anesthesiologists' annual meeting. MEASUREMENTS AND MAIN RESULTS: One hundred fifty anesthesiologists were surveyed on how they use propofol to achieve an antiemetic effect. A large majority (84%) of the anesthesiologists surveyed stated they used propofol for its antiemetic effect: 63% of those used propofol for induction only for cases lasting <1 h to achieve an antiemetic effect. In addition 37% used a "sandwich" technique, using propofol at the beginning and end of a case for a similar purpose. There is evidence that the antiemetic effect of propofol is associated with a defined plasma concentration range; mean, 343 ng/mL (10-90% confidence intervals [CI] 200-600 ng/mL). Simulation data demonstrated that after propofol 2 mg/kg, its concentration will drop below 350 ng/mL at 32 min. After 2 mg/kg and 20 mg within 10 min of the end of surgery, its concentration will drop below 350 ng/mL by 7 min after the 20 mg bolus dose. This finding suggests that the plasma concentrations of propofol, when used in these cases, will be below the effective range of antiemetic effect. CONCLUSIONS: Many anesthesiologists used propofol for its antiemetic effect. There is strong evidence for its antiemetic efficacy after anesthesia maintained by a propofol infusion and also for its use in the postanesthesia care unit (PACU). However, there is little evidence to support its use purely at induction of anesthesia or as part of a "sandwich" technique in an attempt to reduce postoperative nausea and vomiting. This is especially true in cases lasting longer than a few minutes.

A preliminary investigation of remifentanil as a labor analgesic.

IMPLICATIONS: In this preliminary investigation, we evaluated the safety and analgesic efficacy of IV remifentanil for labor pain. Four women were studied, and then the trial was terminated because administration of this novel synthetic opioid produced significant maternal side effects in the absence of effective pain control.

Norwalk virus open reading frame 3 encodes a minor structural protein.

Norwalk virus (NV) is a causative agent of acute epidemic nonbacterial gastroenteritis in humans. The inability to cultivate NV has required the use of molecular techniques to examine the genome organization and functions of the viral proteins. The function of the NV protein encoded by open reading frame 3 (ORF 3) has been unknown. In this paper, we report the characterization of the NV ORF 3 protein expressed in a cell-free translation system and in insect cells and show its association with recombinant virus-like particles (VLPs) and NV virions. Expression of the ORF 3 coding region in rabbit reticulocyte lysates resulted in the production of a single protein with an apparent molecular weight of 23,000 (23K protein), which is not modified by N-linked glycosylation. The ORF 3 protein was expressed in insect cells by using two different baculovirus recombinants; one recombinant contained the entire 3' end of the genome beginning with the ORF 2 coding sequences (ORFs 2+3), and the second recombinant contained ORF 3 alone. Expression from the construct containing both ORF 2 and ORF 3 resulted in the expression of a single protein (23K protein) detected by Western blot analysis with ORF 3-specific peptide antisera. However, expression from a construct containing only the ORF 3 coding sequences resulted in the production of multiple forms of the ORF 3 protein ranging in size from 23,000 to 35,000. Indirect-immunofluorescence studies using an ORF 3 peptide antiserum showed that the ORF 3 protein is localized to the cytoplasm of infected insect cells. The 23K ORF 3 protein was consistently associated with recombinant VLPs purified from the media of insect cells infected with a baculovirus recombinant containing the entire 3' end of the NV genome. Western blot analysis of NV purified from the stools of NV-infected volunteers revealed the presence of a 35K protein as well as multiple higher-molecular-weight bands specifically recognized by an ORF 3 peptide antiserum. These results indicate that the ORF 3 protein is a minor structural protein of the virion.