Closed circuit xenon delivery for 72h in neonatal piglets following hypoxic insult using an ambient pressure automated control system: Development, technical evaluation and pulmonary effects.

BACKGROUND: Therapeutic hypothermia (TH) for 72h is the standard treatment following neonatal encephalopathy (NE). However, one-third do not benefit and adjunctive therapies are urgently needed. Xenon enhances neuroprotection with TH when administered at 50% concentration within 5hours of hypoxia in experimental studies. Delayed initiation (~10 hours of age) of 30% xenon for 24 hours during TH did not improve early adverse biomarkers in a clinical trial of Xenon+TH vs TH. After hypoxia-ischemia, excitotoxic injury via N-methyl-D-aspartate receptor overactivation lasts days. Since xenon partially inhibits this receptor, we hypothesised that giving 50% xenon throughout the entire 72h TH and rewarming periods would enhance neuroprotection. Xenon costs $30/litre, so a closed-circuit breathing system is desirable with automated fresh gas delivery. METHODS: Seven mechanically ventilated newborn pigs were randomized to receive 50% inhaled xenon for 72h during hypothermia (rectal-temperature 35°C) and subsequent rewarming following a global hypoxic-ischemic insult (XeHT, N = 4) or under normothermia for 72h (rectal-temperature 38.5°C) following sham insult (XeNT, N = 3). An automated fresh gas delivery system injected oxygen/air/xenon boluses into a closed-circuit based on measured gas concentrations. RESULTS AND DISCUSSION: Median (IQR) xenon consumption was 0.31 L/h (0.18, 0.50) and 0.34L/h (0.32, 0.49) for hypothermic and normothermic groups respectively, 0.34L/h (0.25, 0.53) overall. 92% of 9626 xenon and 69% of 9635 oxygen measurements were within 20% variation from targets. For xenon concentration, the median absolute performance errors for the XeHT and XeNT groups were 6.14% and 3.84% respectively and 4.31% overall. For oxygen these values were 13.42%, 15.05% and 12.4% respectively. There were no adverse pulmonary pathophysiology findings. Clinical problems over the total period included three related to sensors, seven breathing system leaks, ten partial and one complete tracheal tube occlusion episodes. CONCLUSION: The automated controller functioned as intended maintaining an inhaled xenon concentration close to the 50% target for 72-78h at a xenon cost of $11.1/h.

Real-Time Measurement of Xenon Concentration in a Binary Gas Mixture Using a Modified Ultrasonic Time-of-Flight Anesthesia Gas Flowmeter: A Technical Feasibility Study.

BACKGROUND: Xenon (Xe) is an anesthetic gas licensed for use in some countries. Fractional concentrations (%) of gases in a Xe:oxygen (O2) mixture are typically measured using a thermal conductivity meter and fuel cell, respectively. Speed of sound in such a binary gas mixture is related to fractional concentration, temperature, pressure, and molar masses of the component gases. We therefore performed a study to assess the feasibility of developing a novel single sterilizable device that uses ultrasound time-of-flight to measure both real-time flowmetry and fractional gas concentration of Xe in O2. METHODS: For the purposes of the feasibility study, we adapted an ultrasonic time-of-flight flowmeter from a conventional anesthetic machine to additionally measure real-time fractional concentration of Xe in O2. A total of 5095 readings of Xe % were taken in the range 5%-95%, and compared with simultaneous measurements from the gold standard of a commercially available thermal conductivity Xe analyzer. RESULTS: Ultrasonic measurements of Xe (%) showed agreement with thermal conductivity meter measurements, but there was marked discontinuity in the middle of the measurement range. Bland-Altman analysis (95% confidence interval in parentheses) yielded: mean difference (bias) 3.1% (2.9%-3.2%); lower 95% limit of agreement -4.6% (-4.8% to -4.4%); and upper 95% limit of agreement 10.8% (10.5%-11.0%). CONCLUSIONS: The adapted ultrasonic flowmeter estimated Xe (%), but the level of accuracy is insufficient for clinical use. With further work, it may be possible to develop a device to perform both flowmetry and binary gas concentration measurement to a clinically acceptable degree of accuracy.

Fentanyl Induces Cerebellar Internal Granular Cell Layer Apoptosis in Healthy Newborn Pigs.

BACKGROUND: Opioids like fentanyl are regularly used in neonates for analgesia and sedation. So far, they have been reported to be safe and eligible to use. The cerebellum has become a focus of neurodevelopmental research within the last years, as it is known to play an important role in long-lasting motor, cognitive, and other behavioral changes. The cerebellar cortex is of major importance in the coordinative role of the cerebellum and highly vulnerable to injury and impaired growth. OBJECTIVE: This study was performed to evaluate the apoptotic effect of intravenous fentanyl infusion on the cerebellum in healthy newborn pigs. METHODS: Thirteen healthy pigs (

Retrospective Analysis of Esophageal Heat Transfer for Active Temperature Management in Post-cardiac Arrest, Refractory Fever, and Burn Patients.

Core temperature management is an important aspect of critical care; preventing unintentional hypothermia, reducing fever, and inducing therapeutic hypothermia when appropriate are each tied to positive health outcomes. The purpose of this study is to evaluate the performance of a new temperature management device that uses the esophageal environment to conduct heat transfer. De-identified patient data were aggregated from three clinical sites where an esophageal heat transfer device (EHTD) was used to provide temperature management. The device was evaluated against temperature management guidelines and best practice recommendations, including performance during induction, maintenance, and cessation of therapy. Across all active cooling protocols, the average time-to-target was 2.37 h and the average maintenance phase was 22.4 h. Patients spent 94.9% of the maintenance phase within ±1.0°C and 67.2% within ±0.5°C (574 and 407 measurements, respectively, out of 605 total). For warming protocols, all of the patient temperature readings remained above 36°C throughout the surgical procedure (average 4.66 h). The esophageal heat transfer device met performance expectations across a range of temperature management applications in intensive care and burn units. Patients met and maintained temperature goals without any reported adverse events.

Feasibility of a Miniature Esophageal Heat Exchange Device for Rapid Therapeutic Cooling in Newborns: Preliminary Investigations in a Piglet Model.

Therapeutic hypothermia (TH) after neonatal encephalopathy, commonly provided by 72 hours of whole-body cooling using a wrap, limits parents' physical contact with their infants affecting bonding and may not be suitable for encephalopathic preterm infants with fragile skin. Alternative cooling methods are unavailable for this population. We investigated in a neonatal pig model the feasibility of achieving a 3.5°C reduction in rectal temperature (Trectal) similar to clinical TH protocols from 38.5°C (normothermia for pigs) to a target of 35°C ± 0.2°C, using a novel neonatal esophageal heat exchanger (NEHE), compared its efficacy to passive cooling, and investigated its ability to maintain target Trectal. Ventilated and anesthetized Landrace/Large white newborn pigs had the NEHE inserted. Water at adjustable temperatures and rates flowed down a central tube, returning up a surrounding distensible blind ending latex tube in a continuous loop. An initial experiment guided four subsequent cycles of passive cooling (30 minutes), rewarming to 38.5°C, active esophageal cooling to 35°C ± 0.2°C, active maintenance of target Trectal (30 minutes), and rewarming. We compared surface, rectal temperature, and hemodynamic changes among passive, active, and maintenance phases, and esophageal histopathology against control. Compared with passive cooling, esophageal cooling achieved target Trectal significantly earlier (71.3 minutes vs. 17.25 minutes, p = 0.003) with significantly greater rates of reduction in rectal (p = 0.0002) and surface (p = 0.005) temperatures and heart rate (p = 0.04). A water temperature of 39.1°C-40.2°C at a flow of 108-120 mL/min maintained Trectal around 35°C ± 0.2°C. The higher peak heart rate and blood pressure within 8 minutes of the maintenance phase (p = 0.04) subsequently stabilized. Histopathology showed congestion, edema, and neutrophil infiltration with increasing cycles. Esophageal cooling is feasible and effective in achieving rapid cooling in newborns. Subsequent maintenance at this temperature required continued circulation of warm water. Esophageal histopathology needs further evaluation after 72 hours servo-control cooling with a narrower range of water temperatures in a larger group of animals.

Investigation of Two Prototypes of Novel Noncontact Technologies for Automated Real-Time Capture of Incremental Drug Administration Data From Syringes.

BACKGROUND: An ideal electronic anesthesia recording system would be capable of not only recording physiological data but also injectable drug doses given, including those given incrementally from one syringe, without recourse to manual data entry. We compared 2 prototype devices which wirelessly recognized individual syringes and measured changes in their plunger positions via 2 different optical noncontact means, allowing calculation of incremental drug doses given. METHODS: Both devices incorporated a radio-frequency identification reader, which wirelessly read a unique code from a radio-frequency identification tag within syringe drug labels. A custom-designed cradle oriented any inserted 1-mL to 20-mL syringe in a repeatable position. The "laser" device had a moving laser beam broken by the end of the syringe plunger. The infrared (IR) device measured time of travel of IR light from a sender to a syringe plunger and back to a receiver. Both devices could therefore determine the drug and volume administered since the previous occasion when any syringe had been used. For each syringe size of 1, 2, 5, 10, and 20 mL, 121 plunger-length measurements were made over their full range, with each machine against a reference method of water filling and weighing using a randomized de Bruijn sequence. RESULTS: For every syringe size, the laser device showed greater accuracy and precision, lower bias, and narrower limits of agreement (95% confidence intervals = bias ± 1.96 SD) than the IR device when compared to the reference method. For all syringe sizes, the range of bias was -0.05 to 0.32 mL for the laser and -2.42 to 1.38 mL for the IR. Lin concordance correlation coefficient values for the IR versus reference methods ranged from 0.6259 to 0.9255, with the lowest coefficients seen in syringes with the shortest distance of plunger travel (2 and 5 mL), while in laser versus reference comparisons, these coefficients were similar (0.9641-0.9981) over all syringe lengths. CONCLUSIONS: Both devices measured syringe volume changes, demonstrating potential for measuring incremental drug doses, recording these, and also the time of each measurement. The IR device had no moving parts, which would be advantageous in a clinical situation. However, the current embodiment was not deemed accurate enough for clinical use, potentially remediable through improvements in hardware and software design. The laser device showed high accuracy and precision over all syringe sizes and contained volumes, and was considered potentially accurate enough for clinical use with suitable development.

Use of an Esophageal Heat Exchanger to Maintain Core Temperature during Burn Excisions and to Attenuate Pyrexia on the Burns Intensive Care Unit.

Introduction. Burns patients are vulnerable to hyperthermia due to sepsis and SIRS and to hypothermia due to heat loss during excision surgery. Both states are associated with increased morbidity and mortality. We describe the first use of a novel esophageal heat exchange device in combination with a heater/cooler unit to manage perioperative hypothermia and postoperative pyrexia. Material and Methods. The device was used in three patients with full thickness burns of 51%, 49%, and 45% body surface area to reduce perioperative hypothermia during surgeries of >6 h duration and subsequently to control hyperthermia in one of the patients who developed pyrexia of 40°C on the 22nd postoperative day due to E. coli/Candida septicaemia which was unresponsive to conventional cooling strategies. Results. Perioperative core temperature was maintained at 37°C for all three patients, and it was possible to reduce ambient temperature to 26°C to increase comfort levels for the operating team. The core temperature of the pyrexial patient was reduced to 38.5°C within 2.5 h of instituting the device and maintained around this value thereafter. Conclusion. The device was easy to use with no adverse incidents and helped maintain normothermia in all cases.

Xenon depresses aEEG background voltage activity whilst maintaining cardiovascular stability in sedated healthy newborn pigs.

BACKGROUND: Changes in electroencephalography (EEG) voltage range are used to monitor the depth of anaesthesia, as well as predict outcome after hypoxia-ischaemia in neonates. Xenon is being investigated as a potential neuroprotectant after hypoxic-ischaemic brain injury, but the effect of Xenon on EEG parameters in children or neonates is not known. This study aimed to examine the effect of 50% inhaled Xenon on background amplitude-integrated EEG (aEEG) activity in sedated healthy newborn pigs. METHODS: Five healthy newborn pigs, receiving intravenous fentanyl sedation, were ventilated for 24 h with 50%Xenon, 30%O2 and 20%N2 at normothermia. The upper and lower voltage-range of the aEEG was continuously monitored together with cardiovascular parameters throughout a 1 h baseline period with fentanyl sedation only, followed by 24 h of Xenon administration. RESULTS: The median (IQR) upper and lower aEEG voltage during 1 h baseline was 48.0 µV (46.0-50.0) and 25.0 µV (23.0-26.0), respectively. The median (IQR) aEEG upper and lower voltage ranges were significantly depressed to 21.5 µV (20.0-26.5) and 12.0 µV (12.0-16.5) from 10 min after the onset of 50% Xenon administration (p=0.002). After the initial Xenon induced depression in background aEEG voltage, no further aEEG changes were seen over the following 24h of ventilation with 50% xenon under fentanyl sedation. Mean arterial blood pressure and heart rate remained stable. CONCLUSION: Mean arterial blood pressure and heart rate were not significantly influenced by 24h Xenon ventilation. 50% Xenon rapidly depresses background aEEG voltage to a steady ~50% lower level in sedated healthy newborn pigs. Therefore, care must be taken when interpreting the background voltage in neonates also receiving Xenon.

Evaluation of 2 novel devices for calculation of fluid requirements in pediatric burns.

OBJECTIVES: The Parkland formula for maintenance and resuscitation fluid requirements in the first 24 hours after pediatric burns is widely used, but calculation errors frequently occur. Two different novel aids to calculation, a dedicated electronic device and a mechanical disc calculator, are described and compared with the conventional method of calculation (pen and paper, assisted by a general purpose calculator). METHODS: In a blinded randomized volunteer study, 21 participants performed a total of 189 calculations using simulated patient data to compare the accuracy and speed of 3 different methods for calculating resuscitation fluid requirements based on the pediatric Parkland formula. Bespoke software generated the simulated patient data and recorded accuracy and speed of all participant responses. RESULTS: Sixty-five percent of calculations with the electronic device, 35% using the disc and 44% using the pen/paper methods were within ±5% of the correct value and considered "correct" for clinical purposes. The method used strongly affected the tendency to make errors (logistic regression). With thresholds of error magnitude classed as very small (>5%), small (>25%), medium (>50%) and large (>100%) of the correct value respectively, the electronic method produced fewer errors than both disc and pen/paper methods at all error thresholds. Disc produced more errors than pen/paper at the greater than 5% threshold but fewer at the greater than 25%, greater than 50%, and greater than 100% thresholds. CONCLUSIONS: Both novel devices provide safer and faster alternatives to conventional methods for calculation of fluid requirements in pediatric burns.

Adding 5 h delayed xenon to delayed hypothermia treatment improves long-term function in neonatal rats surviving to adulthood.

BACKGROUND: We previously reported that combining immediate hypothermia with immediate or 2 h delayed inhalation of an inert gas, xenon, gave additive neuroprotection in rats after a hypoxic-ischemic insult, compared to hypothermia alone. Defining the therapeutic time window for this new combined intervention is crucial in clinical practice when immediate treatment is not always feasible. The aim of this study is to investigate whether combined hypothermia and xenon still provide neuroprotection in rats after a 5 h delay for both hypothermia and xenon. METHODS: Seven-day-old Wistar rat pups underwent a unilateral hypoxic-ischemic insult. Pups received 5 h of treatment starting 5 h after the insult randomized between normothermia, hypothermia, or hypothermia with 50% xenon. Surviving pups were tested for fine motor function through weeks 8-10 before being euthanized at week 11. Their hemispheric and hippocampal areas were assessed. RESULTS: Both delayed hypothermia-xenon and hypothermia-only treated groups had significantly less brain tissue loss than those which underwent normothermia. The functional performance after 1 wk and adulthood was significantly better after hypothermia-xenon treatment as compared to the hypothermia-only or normothermia groups. CONCLUSION: Adding 50% xenon to 5 h delayed hypothermia significantly improved functional outcome as compared to delayed hypothermia alone despite similar reductions in brain area.

The feasibility of using a portable xenon delivery device to permit earlier xenon ventilation with therapeutic cooling of neonates during ambulance retrieval.

BACKGROUND: Therapeutic hypothermia is the standard of care after perinatal asphyxia. Preclinical studies show 50% xenon improves outcome, if started early. METHODS: During a 32-patient study randomized between hypothermia only and hypothermia with xenon, 5 neonates were given xenon during retrieval using a closed-circuit incubator-mounted system. RESULTS: Without xenon availability during retrieval, 50% of eligible infants exceeded the 5-hour treatment window. With the transportable system, 100% were recruited. Xenon delivery lasted 55 to 120 minutes, using 174 mL/h (117.5-193.2) (median [interquartile range]), after circuit priming (1300 mL). CONCLUSIONS: Xenon delivery during ambulance retrieval was feasible, reduced starting delays, and used very little gas.

Combined treatment of xenon and hypothermia in newborn rats--additive or synergistic effect?

BACKGROUND: Breathing the inert gas Xenon (Xe) enhances hypothermic (HT) neuroprotection after hypoxia-ischemia (HI) in small and large newborn animal models. The underlying mechanism of the enhancement is not yet fully understood, but the combined effect of Xe and HT could either be synergistic (larger than the two effects added) or simply additive. A previously published study, using unilateral carotid ligation followed by hypoxia in seven day old (P7) rats, showed that the combination of mild HT (35°C) and low Xe concentration (20%), both not being neuroprotective alone, had a synergistic effect and was neuroprotective when both were started with a 4 h delay after a moderate HI insult. To examine whether another laboratory could confirm this finding, we repeated key aspects of the study. DESIGN/METHODS: After the HI-insult 120 pups were exposed to different post-insult treatments: three temperatures (normothermia (NT) NT37°C, HT35°C, HT32°C) or Xe concentrations (0%, 20% or 50%) starting either immediately or with a 4 h delay. To assess the synergistic potency of Xe-HT, a second set (n = 101) of P7 pups were exposed to either HT35°C+Xe0%, NT+Xe20% or a combination of HT35°C+Xe20% starting with a 4 h delay after the insult. Brain damage was analyzed using relative hemispheric (ligated side/unligated side) brain tissue area loss after seven day survival. RESULTS: Immediate HT32°C (p = 0.042), but not HT35°C significantly reduced brain injury compared to NT37°C. As previously shown, adding immediate Xe50% to HT32°C increased protection. Neither 4 h-delayed Xe20%, nor Xe50% at 37°C significantly reduced brain injury (p>0.050). In addition, neither 4 h-delayed HT35°C alone, nor HT35°C+Xe20% reduced brain injury. We found no synergistic effect of the combined treatments in this experimental model. CONCLUSIONS: Combining two treatments that individually were ineffective (delayed HT35°C and delayed Xe20%) did not exert neuroprotection when combined, and therefore did not show a synergistic treatment effect.

Equipotent subanesthetic concentrations of sevoflurane and xenon preventing cold-stimulated vocalization of neonatal rats.

BACKGROUND: The effects of inhaled anesthetics on the developing brain are studied using neonatal rodents exposed to fractions of minimum alveolar concentration (to avoid cardiorespiratory compromise). However, these fractions cannot be assumed to be equipotent. Xenon's anesthetic and neuroprotective properties warrant investigation in these models. Therefore, equipotent, subanesthetic concentrations of inhaled anesthetics are needed. METHODS: Forty-eight Wistar rats (Charles River Laboratories, Kent, United Kingdom) on postnatal day 9 were randomized to eight concentrations of inhaled anesthetics: isoflurane, sevoflurane, or xenon. Exposure was closely monitored in individual metal-based chambers resting on a 35°C mat to maintain normothermia. A 25°C mat was used to stimulate vocalization and a sound recording made (1 min, 1 to 100 kHz). Rectal temperature or partial pressure of carbon dioxide and pH of mixed arteriovenous blood were measured immediately after the exposure. Concentration-response models were constructed using logistic regression (dependent variable: vocalization and explanatory variable: concentration). The effects of all other explanatory variables were assessed by inserting them individually into the model. RESULTS: The effective inhaled concentrations preventing cold-stimulated vocalization in 50 and 95% of neonatal rats (EiC50 and EiC95) on postnatal day 9 were 0.46 and 0.89% sevoflurane and 20.15 and 34.81% xenon, respectively. The effect on the EiC50 of all other explanatory variables, including duration, was minimal. Stability of EiC50 isoflurane was not achieved over three durations (40, 80, and 120 min exposure). Partial pressure of carbon dioxide and pH in mixed arteriovenous blood appeared normal. CONCLUSIONS: The authors report equipotent subanesthetic concentrations of sevoflurane and xenon in neonatal rats with preserved cardiopulmonary function. This may be useful in designing neonatal rodent models of anesthesia.

Sedation management during therapeutic hypothermia for neonatal encephalopathy: atropine premedication for endotracheal intubation causes a prolonged increase in heart rate.

AIM: Heart rate (HR) plays an important role in the assessment of stress during therapeutic hypothermia (TH) for neonatal encephalopathy; we aimed to quantify the effect on HR of endotracheal (ET) intubation and drugs given to facilitate it. If atropine premedication independently increased HR, the main indicator of effective sedation, we hypothesised that increased sedation would have been given. METHODS: Thirty-two, term, neonates recruited into a randomised pilot study comparing TH and TH combined with 50% Xenon inhalation were studied. Indications for ET intubation included: resuscitation at delivery, clinical need and elective re-intubation with a cuffed ET tube if randomised to Xenon. Standard intubation drugs comprised one or more of intravenous morphine, atropine, and suxamethonium. Local cooling guidelines were followed including morphine infusion for sedation. RESULTS: At postnatal hours five to eight atropine increased HR in a linear regression model (p<0.01). All other independent variables were excluded. Where more than one dose of atropine was given total morphine sedation given up to 8h into the treatment period was significantly higher (p<0.01). CONCLUSION: We have shown that atropine premedication for ET intubation significantly increased HR, the main indicator of effective sedation and total morphine dose for sedation during early TH was increased where more than one dose of atropine was given. Bradycardia was not reported in any neonate, even without atropine premedication. We suggest that the use of atropine as part of standard premedication for ET intubation of term neonates undergoing TH should be reconsidered.

Xenon ventilation during therapeutic hypothermia in neonatal encephalopathy: a feasibility study.

BACKGROUND AND OBJECTIVES: Therapeutic hypothermia has become standard of care in newborns with moderate and severe neonatal encephalopathy; however, additional interventions are needed. In experimental models, breathing xenon gas during cooling offers long-term additive neuroprotection. This is the first xenon feasibility study in cooled infants. Xenon is expensive, requiring a closed-circuit delivery system. METHODS: Cooled newborns with neonatal encephalopathy were eligible for this single-arm, dose-escalation study if clinically stable, under 18 hours of age and requiring less than 35% oxygen. Xenon duration increased stepwise from 3 to 18 hours in 14 subjects; 1 received 25% xenon and 13 received 50%. Respiratory, cardiovascular, neurologic (ie, amplitude-integrated EEG, seizures), and inflammatory (C-reactive protein) effects were examined. The effects of starting or stopping xenon rapidly or slowly were studied. Three matched control subjects per xenon treated subject were selected from our cooling database. Follow-up was at 18 months using mental developmental and physical developmental indexes of the Bayley Scales of Infant Development II. RESULTS: No adverse respiratory or cardiovascular effects, including post-extubation stridor, were seen. Xenon increased sedation and suppressed seizures and background electroencephalographic activity. Seizures sometimes occurred during rapid weaning of xenon but not during slow weaning. C-reactive protein levels were similar between groups. Hourly xenon consumption was 0.52 L. Three died, and 7 of 11 survivors had mental and physical developmental index scores ≥70 at follow-up. CONCLUSIONS: Breathing 50% xenon for up to 18 hours with 72 hours of cooling was feasible, with no adverse effects seen with 18 months' follow-up.

A cost-effective and simple electronic solution to communication with patients with tracheostomy in a burns and intensive care setting.

INTRODUCTION AND AIMS: Ventilated patients in ITU (intensive treatment unit) tend to be challenging to communicate with, especially patients who are being weaned. These patients usually have tracheostomy in situ and use means such as writing or letter boards to communicate. The situation becomes complex in patient groups that have burn injuries with bulky dressings and restricted upper limb function. We demonstrate a low cost, easy to use, potentially disposable system that can display words on any television screen via patient input device for such patient groups. MATERIALS AND METHODS: The system consists of input device incorporated with Arduino microcontroller (an open-source electronics prototyping platform based on easy-to-use hardware and software intended for creating interactive environments) and 4 generously oversized control buttons. These are used to control the cursor movements (up, down, left, right) while a fifth has a "select" function. These are large enough to be pressed by an entire bandaged hand using gross upper limb movements only. A standard television is used to display menu containing the 26 letters of the alphabet and a flashing cursor. The patient selects the required letters/icon by moving the cursor and the words so created are displayed along the lower part of the screen for the carers to read. It is envisaged that anyone with basic craft skills should be able to construct this device. CONCLUSION: This device is a self-contained, cost-effective, simple, and open-source system that can be used effectively to bridge the communication gap with significant potential for patient care globally.

Effects of xenon and hypothermia on cerebrovascular pressure reactivity in newborn global hypoxic-ischemic pig model.

Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between -1 and +1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO2, seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx >0.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as 'severe' or 'mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P=0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P=0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, -0.098 (95% CI (-0.18, -0.01)), independent of the insult severity.

Neither xenon nor fentanyl induces neuroapoptosis in the newborn pig brain.

BACKGROUND: Some inhalation anesthetics increase apoptotic cell death in the developing brain. Xenon, an inhalation anesthetic, increases neuroprotection when combined with therapeutic hypothermia after hypoxic-ischemic brain injury in newborn animals. The authors, therefore, examined whether there was any neuroapoptotic effect of breathing 50% xenon with continuous fentanyl sedation for 24 h at normothermia or hypothermia on newborn pigs. METHODS: Twenty-six healthy pigs (<24-h old) were randomized into four groups: (1) 24 h of 50% inhaled xenon with fentanyl at hypothermia (Trec = 33.5 °C), (2) 24 h of 50% inhaled xenon with fentanyl at normothermia (Trec = 38.5 °C), (3) 24 h of fentanyl at normothermia, or (4) nonventilated juvenile controls at normothermia. Five additional nonrandomized pigs inhaled 2% isoflurane at normothermia for 24 h to verify any proapoptotic effect of inhalation anesthetics in our model. Pathological cells were morphologically assessed in cortex, putamen, hippocampus, thalamus, and white matter. To quantify the findings, immunostained cells (caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphate nick-end labeling) were counted in the same brain regions. RESULTS: For groups (1) to (4), the total number of apoptotic cells was less than 5 per brain region, representing normal developmental neuroapoptosis. After immunostaining and cell counting, regression analysis showed that neither 50% xenon with fentanyl nor fentanyl alone increased neuroapoptosis. Isoflurane caused on average a 5- to 10-fold increase of immunostained cells. CONCLUSION: At normothermia or hypothermia, neither 24 h of inhaled 50% xenon with fentanyl sedation nor fentanyl alone induces neuroapoptosis in the neonatal pig brain. Breathing 2% isoflurane increases neuroapoptosis in neonatal pigs.