Short- and Long-Term Outcome in Critically Ill Children After Acute Interhospital Transport to a PICU in Sweden.

OBJECTIVES: Data on long-term survival in children after interhospital transport to a PICU are scarce. The main objective was to investigate short- and long-term outcome after acute interhospital transport to a PICU for different age and risk stratification groups. Secondary aims were to investigate whether neonatal patients would have higher mortality and be more resource demanding than older patients. DESIGN: Single-center, retrospective cohort study. SETTING: Specialist pediatric transport team and a tertiary PICU in Sweden. PATIENTS: Critically ill children 0-18 years old, acutely transported by a specialist pediatric transport team to a PICU in Sweden (January 1, 2008, to December 31, 2016). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 401 acute transport events were included. Overall mortality was 15.7% with a median follow-up time of 3.4 years (range, 0-10.2 yr). Median predicted death rate was 4.9%. There was no mortality during transport. Cumulative mortality almost doubled within the first 6 months after PICU discharge, from 6.5% to 12.0%. Of late deaths, 66.7% occurred in the risk stratification group predicted death rate 0-10%, and 95% suffered from severe comorbidity. There were no deaths after PICU discharge in the neonatal group. Cumulative mortality in multiple transported patients was 36.4%. CONCLUSIONS: This is the first report on long-term survival after acute pediatric interhospital transport. For the entire cohort, there was significant mortality after PICU discharge, especially in multiple transported patients. In contrast, survival in the subgroup of neonatal patients was high after PICU discharge.

Unnecessary harm is avoided by reliable paediatric index of mortality2 scores without arterial gas sampling.

AIM: To investigate whether unnecessary harm could be avoided in children admitted to paediatric intensive care (PICU), we analysed the impact of arterial blood gas on the paediatric index of mortality score2 (PIM2) and the derived predicted death rate (PDR). METHODS: From January 1, 2008 to December 31, 2010, 1793 consecutive admissions, newborn infants to 16 years of age (median 0.71 years) from a single, tertiary PICU in Gothenburg Sweden, were collected. Admission information on arterial oxygen tension (PaO2 ) and fraction of inspired oxygen (FiO2 ) was extracted from 990 admissions. RESULTS: There was close agreement between PIM2 score and PDR regardless of whether the PaO2 /FiO2 ratio was omitted or not. In the subgroup of admissions with a respiratory admission diagnosis, the inclusion of the PaO2 /FiO2 ratio increased the accuracy of the PIM2 score as well as the PDR. The standard mortality ratio was slightly but not significantly overestimated by excluding the PaO2 /FiO2 ratio. CONCLUSION: To avoid unnecessary harm to children admitted to PICU, an arterial blood gas analysis should only be performed if clinically indicated or if the child has a respiratory admission diagnosis. Estimation of the PIM2 score and PDR will not be less accurate by this approach.

Standardized Unloading of Respiratory Muscles during Neurally Adjusted Ventilatory Assist: A Randomized Crossover Pilot Study.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Currently, there is no standardized method to set the support level in neurally adjusted ventilatory assist (NAVA). The primary aim was to explore the feasibility of titrating NAVA to specific diaphragm unloading targets, based on the neuroventilatory efficiency (NVE) index. The secondary outcome was to investigate the effect of reduced diaphragm unloading on distribution of lung ventilation. METHODS: This is a randomized crossover study between pressure support and NAVA at different diaphragm unloading at a single neurointensive care unit. Ten adult patients who had started weaning from mechanical ventilation completed the study. Two unloading targets were used: 40 and 60%. The NVE index was used to guide the titration of the assist in NAVA. Electrical impedance tomography data, blood-gas samples, and ventilatory parameters were collected. RESULTS: The median unloading was 43% (interquartile range 32, 60) for 40% unloading target and 60% (interquartile range 47, 69) for 60% unloading target. NAVA with 40% unloading led to more dorsal ventilation (center of ventilation at 55% [51, 56]) compared with pressure support (52% [49, 56]; P = 0.019). No differences were found in oxygenation, CO2, and respiratory parameters. The electrical activity of the diaphragm was higher during NAVA with 40% unloading than in pressure support. CONCLUSIONS: In this pilot study, NAVA could be titrated to different diaphragm unloading levels based on the NVE index. Less unloading was associated with greater diaphragm activity and improved ventilation of the dependent lung regions.

Performance of regional oxygen saturation monitoring by near-infrared spectroscopy (NIRS) in pediatric inter-hospital transports with special reference to air ambulance transports: a methodological study.

The aim of the present study was to evaluate the performance of regional oxygen saturation (rSO2) monitoring with near infrared spectroscopy (NIRS) during pediatric inter-hospital transports and to optimize processing of the electronically stored data. Cerebral (rSO2-C) and abdominal (rSO2-A) NIRS sensors were used during transport in air ambulance and connecting ground ambulance. Data were electronically stored by the monitor during transport, extracted and analyzed off-line after the transport. After removal of all zero and floor effect values, the Savitzky-Golay algorithm of data smoothing was applied on the NIRS-signal. The second order of smoothing polynomial was used and the optimal number of neighboring points for the smoothing procedure was evaluated. NIRS-data from 38 pediatric patients was examined. Reliability, defined as measurements without values of 0 or 15%, was acceptable during transport (> 90% of all measurements). There were, however, individual patients with < 90% reliable measurements during transport, while no patient was found to have < 90% reliable measurements in hospital. Satisfactory noise reduction of the signal, without distortion of the underlying information, was achieved when 20-50 neighbors ("window-size") were used. The use of NIRS for measuring rSO2 in clinical studies during pediatric transport in ground and air-ambulance is feasible but hampered by unreliable values and signal interference. By applying the Savitzky-Golay algorithm, the signal-to-noise ratio was improved and enabled better post-hoc signal evaluation.

Characteristics and outcomes of critically ill children following emergency transport by a specialist paediatric transport team.

AIM: We compared acute patients admitted to a single paediatric intensive care unit (PICU) following an emergency transfer by a specialist paediatric transport team and by other routes. METHODS: This was a retrospective descriptive register-based study of consecutive admissions to a tertiary PICU in Sweden from 1 January 2008 to 31 December 2013. We compared the general characteristics of the cohorts, together with predicted death rates (PDR), PICU mortality, 30-day mortality, PICU length of stay (PICU LOS) and resource use. RESULTS: Of the 3665 nonelective admissions, 221 patients received emergency transport from referring hospitals to the PICU by the specialist paediatric transport team. Their median age was lower (146 versus 482 days), PDR was higher (5.58% versus 1.39%), PICU LOS was longer (4.24 days versus 1.06 days), and they received more PICU-specific therapies. The standardised mortality ratio did not differ between the cohorts, and the PICU mortality was lower than predicted in both groups. The transport distance and mode of transport did not influence survival. CONCLUSION: Children admitted to the PICU following emergency transfers by the specialist paediatric transport team were younger, sicker, received more PICU-specific therapies and had longer PICU LOS than other acutely admitted critically ill patients. This indicates that these transfers were appropriate.

Neurally adjusted ventilatory assist feasibility during anaesthesia: A randomised crossover study of two anaesthetics in a large animal model.

BACKGROUND: Spontaneous breathing during mechanical ventilation improves gas exchange by redistribution of ventilation to dependent lung regions. Neurally adjusted ventilatory assist (NAVA) supports spontaneous breathing in proportion to the electrical activity of the diaphragm (EAdi). NAVA has never been used in the operating room and no studies have systematically addressed the influence of different anaesthetic drugs on EAdi. OBJECTIVES: The aim of this study was to test the feasibility of NAVA under sedation and anaesthesia with two commonly used anaesthetics, sevoflurane and propofol, with and without remifentanil, and to study their effects on EAdi and breathing mechanics. DESIGN: A crossover study with factorial design of NAVA during sedation and anaesthesia in pigs. SETTING: University basic science laboratory in Uppsala, Sweden, from March 2009 to February 2011. ANIMALS: Nine juvenile pigs were used for the experiment. INTERVENTIONS: The lungs were ventilated using NAVA while the animals were sedated and anaesthetised with continuous low-dose ketamine combined with sevoflurane and propofol, with and without remifentanil. MAIN OUTCOME MEASURES: During the last 5  min of each study period (total eight steps) EAdi, breathing pattern, blood gas analysis, neuromechanical efficiency (NME) and neuroventilatory efficiency (NVE) during NAVA were determined. RESULTS: EAdi was preserved and normoventilation was reached with both sevoflurane and propofol during sedation as well as anaesthesia. Tidal volume (Vt) was significantly lower with sevoflurane anaesthesia than with propofol. NME was significantly higher with sevoflurane than with propofol during anaesthesia with and without remifentanil. NVE was significantly higher with sevoflurane than with propofol during sedation and anaesthesia. CONCLUSION: NAVA is feasible during ketamine-propofol and ketamine-sevoflurane anaesthesia in pigs. Sevoflurane promotes lower Vt, and affects NME and NVE less than propofol. Our data warrant studies of NAVA in humans undergoing anaesthesia.

EMD 57033 partially reverses ventilator-induced diaphragm muscle fibre calcium desensitisation.

In critically ill patients, ventilator-induced diaphragm muscle fibre dysfunction (VIDD) contributes to weaning problems, increasing hospitalisation time and related costs. VIDD pathophysiology remains partially unknown, especially the characterisation of the contractile dysfunction. In the present study, it was hypothesised that Ca(2+) activation is affected during VIDD. Ca(2+) sensitivity of contraction was therefore evaluated at the single skinned diaphragm muscle fibre level in piglets randomised into sham operation or 5-day mechanical ventilation. Ca(2+) sensitivities of force and stiffness in fibres were significantly impaired in all mechanically ventilated piglets compared with sham-operated controls, suggesting a less efficient Ca(2+) activation of cells, i.e. a lower relative number of strongly attached cross-bridges for each sub-maximal concentration of Ca(2+). In an attempt to test whether this negative effect of VIDD is reversible, single muscle fibres were exposed to the EMD 57033 Ca(2+) sensitiser. EMD 57033 (30 microM) improved the Ca(2+) sensitivity of force and stiffness in fibres from animals that were mechanically ventilated for 5 days as well as in sham-operated piglets. Thus, EMD 57033 partly restored the Ca(2+) activation of cells, reducing VIDD. This finding offers a strong basis for evaluating the effect of Ca(2+) sensitisers on diaphragm function in vivo.

Influence of altitude on cerebral and splanchnic oxygen saturation in critically ill children during air ambulance transport.

OBJECTIVE: The aim of the current study was to investigate how cerebral and splanchnic oxygen saturation (rSO2-C and rSO2-A) in critically ill children transported in air ambulance was affected by flight with cabin pressurization corresponding to ≥ 5000 feet. A second aim was to investigate any differences between cyanotic and non-cyanotic children in relation to cerebral and splanchnic oxygen saturation during flight ≥ 5000 feet. The variability of the cerebral and splanchnic Near Infrared Spectroscopy (NIRS) sensors was evaluated. DESIGN: NIRS was used to measure rSO2-C and rSO2-A during transport of critically ill children in air ambulance. rSO2 data was collected and stored by the NIRS monitor and extracted and analyzed off-line after the transport. Prior to evaluation of the NIRS signals all zero and floor-effect values were removed. SETTING: The Pediatric Intensive Care Unit (PICU) at Astrid Lindgren Children's Hospital, Karolinska University Hospital in Stockholm, Sweden. PATIENTS: In total, 44 critically ill children scheduled for inter-hospital transport by a specialized pediatric transport team were included in the study between January 2014 and January 2019 (convenience sampling). INTERVENTION: No interventions were conducted. MEASUREMENTS: All study patients were monitored with a cerebral NIRS-sensor placed over the forehead and an abdominal NIRS-sensor placed in the infra-umbilical area for cerebral and splanchnic regional oxygen saturation monitoring, rSO2-C and rSO2-A, respectively. MAIN RESULTS: Complete rSO2-C and rSO2-A data was obtained in 39 patients. Median age was 12 days. Cyanotic congenital heart malformations were present in 9 patients (23%). In 22 patients (56%) rSO2-C decreased at altitude ≥ 5000 feet and in 24 patients (61%) rSO2-A decreased at altitude ≥ 5000 feet compared to baseline (p<0.0001). In 25 patients (64%) the rSO2-C/rSO2-A ratio was greater at altitude ≥ 5000 feet than at baseline. A ratio ≥ 1 was seen in 77% of patients at altitude ≥ 5000 feet compared to in 67% of patients at baseline. CONCLUSION: Both cerebral and splanchnic oxygen saturation decreased at altitude ≥ 5000 feet compared to baseline. In most patients, both cyanotic and non-cyanotic, cerebral oxygen saturation was preserved more than splanchnic oxygen saturation.

Short- and long-term follow-up of intensive care unit patients after sedation with isoflurane and midazolam--a pilot study.

OBJECTIVE: To compare memories from the intensive care unit (ICU) and short- and long-term psychological morbidity in patients after sedation with intravenous midazolam or inhaled isoflurane. DESIGN: Prospective long-term follow-up after randomized controlled trial. SETTING: General ICU at Karolinska University Hospital, Solna, Stockholm. PATIENTS: Forty patients in need of sedation during ventilator treatment. INTERVENTIONS: Patients were randomized to receive isoflurane or midazolam for goal-directed sedation until extubation or for a maximum of 96 hrs. MEASUREMENTS AND MAIN RESULTS: For short-term follow-up, doctors', nurses', and physiotherapists' notes from the 4 days following exposure to the study drugs were reviewed for words indicating adequate or pathologic cognitive and psychological recovery. For long-term follow-up, all 6-month survivors received questionnaires including the ICU Memory Tool (ICU-MT), Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), and Well-Being Index. Additionally, several screening questions for previous posttraumatic stress symptoms were included. In the short term follow-up, no significant differences were found between groups. In the long-term follow-up, a trend toward fewer hallucinations/delusions after isoflurane sedation than after midazolam (two of ten isoflurane patients vs. five of seven midazolam patients) was found (p = .06). None of the five solely isoflurane-sedated patients reported hallucinations/delusions from the ICU. There was no difference in groups in long-term psychological morbidity as measured with HADS and IES. Memories of negative feelings in the ICU (ICU-MT) were associated with high HADS and IES scores (Fisher's exact test, p = .02 and p = .01, respectively). CONCLUSIONS: Sedation of ICU patients with isoflurane may result in fewer delusional memories or hallucinations from the ICU compared with more commonly used intravenous sedation. Memories of negative feelings from the ICU were associated with symptoms of depression or anxiety or symptoms indicating posttraumatic stress disorder. Further study of memory and cognitive/psychological recovery after prolonged isoflurane sedation beyond 96 hrs is warranted.

Effects of prolonged mechanical ventilation and inactivity on piglet diaphragm function.

OBJECTIVES: Muscle weakness is associated with immobilization, prolonged mechanical ventilation, critical illness and various critical care therapies. This study used an animal model simulating the critical care environment to investigate the effects of 5 days' mechanical ventilation and inactivity on diaphragm contractility and neurophysiologic function. DESIGN: Prospective laboratory study. SETTING: Animal research laboratory. SUBJECTS: Seven 2-3 month old piglets weighing 20-25 kg. INTERVENTIONS: The animals received constant-flow, volume-controlled mechanical ventilation (Tv 12-15 ml/kg, PEEP 3-5 cmH2O, I:E 1:2) and sedation without paralysis, and spontaneous breathing efforts were prevented. Evoked diaphragm contractions were achieved by transvenous phrenic nerve pacing. MEASUREMENTS AND MAIN FINDINGS: Transdiaphragmatic pressure (Pdi) measurements were used to assess force frequency relationships. Evoked electrophysiologic measures included lowest stimulus threshold and latency, compound muscle action potential (CMAP) amplitude and duration, and amplitude during repetitive nerve stimulation at 3 Hz. Lung function measures included airway pressures, tidal and minute volumes, and dynamic compliance and resistance. There were no clinically significant changes in hemodynamics, oxygenation or ventilation. Indirect measures of lung volume remained stable. Pdi decreased by 20% at all frequencies tested and was accompanied by a 30% decrease in evoked CMAP amplitude, (6.7+/-4.7 mV to 4.5+/-3.9 mV, p=0.01) while CMAP threshold, latency and duration were unchanged and no significant decrement in amplitude was seen during repetitive stimulation at 3 Hz. CONCLUSION: In this in-vivo model of prolonged mechanical ventilation in an intensive caring setting, 5 days of mechanical ventilation with sedation and complete diaphragm inactivity resulted in disturbed diaphragm contractility and activation, while nerve conduction and neuromuscular transmission were not affected. Based on these findings, it is likely that the changes seen occur at the level of peripheral muscle.

Factors underlying the early limb muscle weakness in acute quadriplegic myopathy using an experimental ICU porcine model.

The basic mechanisms underlying acquired generalized muscle weakness and paralysis in critically ill patients remain poorly understood and may be related to prolonged mechanical ventilation/immobilization (MV) or to other triggering factors such as sepsis, systemic corticosteroid (CS) treatment and administration of neuromuscular blocking agents (NMBA). The present study aims at exploring the relative importance of these factors by using a unique porcine model. Piglets were all exposed to MV together with different combinations of endotoxin-induced sepsis, CS and NMBA for five days. Peroneal motor nerve conduction velocity and amplitude of the compound muscle action potential (CMAP) as well as biceps femoris muscle biopsy specimens were obtained immediately after anesthesia on the first day and at the end of the 5-day experimental period. Results showed that peroneal nerve motor conduction velocity is unaffected whereas the size of the CMAP decreases independently of the type of intervention, in all groups after 5 days. Otherwise, despite a preserved size, muscle fibre specific force (maximum force normalized to cross-sectional area) decreased dramatically for animals exposed to MV in combination with CS or/and sepsis. These results suggest that the rapid declines in CMAP amplitude and in force generation capacity are triggered by independent mechanisms with significant clinical and therapeutic implications.

Diaphragm muscle weakness in an experimental porcine intensive care unit model.

In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit.

Three cases of PICU sedation with isoflurane delivered by the 'AnaConDa'.

Prolonged sedation in the pediatric intensive care unit may be difficult because of tolerance, drug dependence and withdrawal, drug interactions and unwanted drug effects. We present three patients sedated with isoflurane via the Anesthetic Conserving Device, AnaConDa. AnaConDa is a modified heat and moisture exchanger that allows evaporation and delivery of inhalational anesthetics without an anesthesia machine, vaporizer or adapted ventilator. Two patients with abdominal complications and prolonged sedation for mechanical ventilation were converted to isoflurane sedation for several days. The third patient with refractory status epilepticus received isoflurane to treat epileptiform electroencephalogram activity. Patients weighing 40 and 30 kg were treated with AnaConDa placed at the Y-piece, while the patient weighing 20 kg was treated with AnaConDa in the inspiratory limb of the respiratory circuit. Adequate sedation was achieved with endtidal isoflurane concentration of 0.3-0.4%, while antiepileptic effect was achieved at a higher dose, 0.9%. Intravenous sedatives could be reduced or discontinued during isoflurane sedation. Inhaled sedation of isoflurane with AnaConDa was effective in these patients. It may provide an alternative in difficult cases needing prolonged sedation and should be evaluated further.

Ambient isoflurane pollution and isoflurane consumption during intensive care unit sedation with the Anesthetic Conserving Device.

OBJECTIVE: To examine ambient isoflurane pollution, scavenging efficacy, and isoflurane consumption using the Anesthetic Conserving Device (ACD) for prolonged isoflurane sedation in the intensive care unit. DESIGN: Prospective observational study. SETTING: Multidisciplinary university intensive care unit. PATIENTS: Fifteen adult ventilator-dependent intensive care unit patients sedated with isoflurane for 12-96 hrs. INTERVENTIONS: Isoflurane was infused to the ACD for sedation of study subjects. Changing of the ACD, isoflurane syringe, and opening of the respiratory circuit were performed in a standardized fashion according to investigator instructions. Active scavenging of waste gas from the ventilator was performed in ten patients; in five patients no active scavenging was performed. MEASUREMENTS AND MAIN RESULTS: Continuous spectrophotometric measurement of ambient isoflurane pollution in parts per million (ppm) at 0.5 m from the patient's head and passive lapel dosimeter sampling for ten staff nurses over 8-hr shifts. Isoflurane requirement and agent consumption were registered in all patients. Spectrophotometric readings (0.1 +/- 0.2 ppm) were well below internationally recommended long-term exposure limits in all cases. Isoflurane peaks during nursing procedures were brief, infrequent, and of low amplitude. There was no observed difference between isoflurane trace levels with or without an active scavenging system in use. Passive dosimeter values were also low, ranging from undetectable to 0.16 ppm. Mean isoflurane consumption was 2.1 +/- 1.0 mL/hr. This is approximately one fourth of predicted and previously reported consumption of isoflurane with vaporizer-administered sedation in the intensive care unit setting. CONCLUSIONS: In the present setting, isoflurane via the ACD is an environmentally safe method of sedation provided users follow instructions for standardizing procedures with potential spillage of isoflurane. This method of sedation requires considerably less isoflurane than with traditional vaporizer technique.

Prolonged isoflurane sedation of intensive care unit patients with the Anesthetic Conserving Device.

OBJECTIVE: To test the efficacy and patient safety of a new method for administering isoflurane for prolonged sedation in the intensive care unit. DESIGN: Randomized controlled trial. SETTING: Multidisciplinary university intensive care unit, January 2002 to July 2003. PATIENTS: Forty ventilator-dependent intensive care unit patients 18-80 yrs old, expected to need >12 hrs sedation. INTERVENTIONS: Patients were randomized to sedation with inhaled isoflurane via the Anesthetic Conserving Device or intravenous midazolam infusion. Study duration was 96 hrs or until extubation. MEASUREMENTS AND MAIN RESULTS: Primary end points were wake-up times from termination of sedative administration and proportion of time within a predefined desired interval on a sedation scale (Bloomsbury Sedation Score). Practical and patient-related complications with the Anesthetic Conserving Device were noted. Hemodynamic, hepatic, and renal side effects were monitored. Wake-up times were significantly shorter in the isoflurane group than in the control group (time to extubation [mean +/- sd] 10 +/- 5 vs. 252 +/- 271 mins, time to follow verbal command 10 +/- 8 vs. 110 +/- 132 mins). Proportion of time within the desired sedation interval was comparable between groups (isoflurane 54%, midazolam 59% of sedation time). Few minor practical problems with this new method for isoflurane administration were noted. No serious complications related to either sedative drug occurred. We found no hemodynamic, hepatic, or renal adverse effects related to either sedative protocol. CONCLUSIONS: Isoflurane via the Anesthetic Conserving Device is a safe and efficacious method for sedation in the intensive care unit, with short wake-up times after termination of administration. The Anesthetic Conserving Device allows easily titratable administration of isoflurane without costly equipment and can be safely managed by nursing staff.