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 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.

Quality of pediatric anesthesia: A cross-sectional study of a university hospital in a low-income country.

OBJECTIVE: To evaluate the quality of pediatric anesthesia in a university hospital in Dar es Salaam, Tanzania. METHOD: A cross-sectional study conducted using a new tool that was developed from the literature and WHO recommendations including 28 parameters as standards for pediatric anesthesia. These 28 parameters consisted of 17 structure parameters of the equipment and medicines that should be present in theatre before any surgery starts, and 11 process parameters of actions taken by staff. Adverse events occurring during the anesthesia were recorded. RESULTS: 30 patients were included, aged between 1.5 months to 5 years with a mean of 2.4 years. 26 of the patients underwent elective surgery and 4 patients emergency surgery. Nine parameters were always present and one parameter (bag and mask) was not available for any of the patients. The structure index ranged from 71% to 94% with a mean of 84%. The process index had a mean score of 71% with a range from 50% to 90%: lower than the structure index (p<0.001). With the structure and process index combined the average score was 79% with a low of 67% and high of 89%. 70 adverse events were observed with a range from 0 to 7 adverse events per patient. The most common adverse event was hypoxia at extubation in 20 (69%) patients. Nine patients had an episode of severe hypoxia at extubation. CONCLUSION: Pediatric anesthesia in low resource settings suffers from deficiencies in the structures and processes of providing good quality care. Improvement efforts may be best focused on improving the consistency and quality of the process of care and a reduction in adverse events rather than the structures available. Use of the assessment tool developed for this research could be useful for systematic quality-improvement efforts and to assess the needs in different settings.

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.

Improving Survival and Neurologic Function for Younger Age Groups After Out-of-Hospital Cardiac Arrest in Sweden: A 20-Year Comparison.

OBJECTIVE: To describe changes in the epidemiology of out-of-hospital cardiac arrest in Sweden with the emphasis on the younger age groups. DESIGN: Prospective observational study. SETTING: Sweden. PATIENTS: Patients were recruited from the Swedish Registry of Cardiopulmonary Resuscitation from 1990 to 2012. Only non-crew-witnessed cases were included. INTERVENTION: Cardiopulmonary resuscitation. MEASUREMENT AND MAIN RESULTS: The endpoint was 30-day survival. Cerebral function among survivors was estimated according to the cerebral performance category scores. In all, 50,879 patients in the survey had an out-of-hospital cardiac arrest, of which 1,321 (2.6%) were 21 years old or younger and 1,543 (3.0%) were 22-35 years old. On the basis of results from 2011 and 2012, we estimated that there are 4.9 cases per 100,000 person-years in the age group 0-21 years. The highest survival was found in the 13- to 21-year age group (12.6%). Among patients 21 years old or younger, the following were associated with an increased chance of survival: increasing age, male gender, witnessed out-of-hospital cardiac arrest, ventricular fibrillation, and a short emergency medical service response time. Among patients 21 years old or younger , there was an increase in survival from 6.2% in 1992-1998 to 14.0% in 2007-2012. Among 30-day survivors, 91% had a cerebral performance category score of 1 or 2 (good cerebral performance or moderate cerebral disability) at hospital discharge. CONCLUSIONS: In Sweden, among patients 21 years old or younger, five out-of-hospital cardiac arrests per 100,000 person-years occur and survival in this patient group has more than doubled during the past two decades. The majority of survivors have good or relatively good cerebral function.

Impaired autophagy, chaperone expression, and protein synthesis in response to critical illness interventions in porcine skeletal muscle.

Critical illness myopathy (CIM) is characterized by a preferential loss of the motor protein myosin, muscle wasting, and impaired muscle function in critically ill intensive care unit (ICU) patients. CIM is associated with severe morbidity and mortality and has a significant negative socioeconomic effect. Neuromuscular blocking agents, corticosteroids, sepsis, mechanical ventilation, and immobilization have been implicated as important risk factors, but the causal relationship between CIM and the risk factors has not been established. A porcine ICU model has been used to determine the immediate molecular and cellular cascades that may contribute to the pathogenesis prior to myosin loss and extensive muscle wasting. Expression profiles have been compared between pigs exposed to the ICU interventions, i.e., mechanically ventilated, sedated, and immobilized for 5 days, with pigs exposed to critical illness interventions, i.e., neuromuscular blocking agents, corticosteroids, and induced sepsis in addition to the ICU interventions for 5 days. Impaired autophagy as well as impaired chaperone expression and protein synthesis were observed in the skeletal muscle in response to critical illness interventions. A novel finding in this study is impaired core autophagy machinery in response to critical illness interventions, which when in concert with downregulated chaperone expression and protein synthesis may collectively affect the proteostasis in skeletal muscle and may exacerbate the disease progression in CIM.

Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model.

Severe muscle wasting is a debilitating condition in critically ill intensive care unit (ICU) patients, characterized by general muscle weakness and dysfunction, resulting in a prolonged mobilization, delayed weaning from the ventilator, and a decreased quality of life post-ICU. The mechanisms underlying limb muscle weakness in ICU patients are complex and involve the impact of primary disease, but also factors common to critically ill ICU patients such as sepsis, mechanical ventilation (MV), immobilization, and systemic administration of corticosteroids (CS). These factors may have additive negative effects on skeletal muscle structure and function, but their respective role alone remain unknown. The primary aim of this study was to examine how CS administration potentiates ventilator and immobilization-related limb muscle dysfunction at the gene level. Comparing biceps femoris gene expression in pigs exposed to MV and CS for 5 days with only MV pigs for the same duration of time showed a distinct deregulation of 186 genes according to microarray. Surprisingly, the decreased force-generation capacity at the single muscle fiber reported in response to the addition of CS administration in mechanically ventilated and immobilized pigs was not associated with an additional upregulation of proteolytic pathways. On the other hand, an altered expression of genes regulating kinase activity, cell cycle, transcription, channel regulation, oxidative stress response, cytoskeletal, sarcomeric, and heat shock protein, as well as protein synthesis at the translational level, appears to play an additive deleterious role for the limb muscle weakness in immobilized ICU patients.

Role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model.

Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover, the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin-induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis, for 5 days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of > 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity, and transcriptional regulation. Genes involved in the regulation of the oxidative stress response and cytoskeletal/sarcomeric and heat shock proteins were on the other hand downregulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients, and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.

Postoperative regional distribution of pulmonary ventilation and perfusion in infants with congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Advances in management of patients with congenital diaphragmatic hernia (CDH) have improved mortality rates but with a risk of increased pulmonary morbidity. The prognosis for CDH survivors remains difficult to predict owing to the lack of adequate methods. We used single photon emission computed tomography (SPECT) to measure the regional distribution of ventilation and perfusion in CDH infants to quantify the degree of lung function impairment and relate it to neonatal clinical disease severity. METHODS: Single photon emission computed tomography was performed in 12 CDH infants at the mean age of six months. Ventilation and perfusion were traced with 5 MBq Technegas and technetium-labelled albumin macro-aggregates, respectively. Neonatal clinical data collected during the patient's stay in the pediatric intensive care unit was correlated with the SPECT data. RESULTS: Single photon emission computed tomography revealed varying degrees of ventilation-perfusion abnormalities which correlated with the presence of pulmonary artery hypertension, days on ventilator and days on extracorporeal membrane oxygenation. CONCLUSIONS: The grade of clinical disease severity in infants following CDH repair is closely related to the ventilation-perfusion abnormality as seen using SPECT. The persistence of pulmonary artery hypertension into the postoperative neonatal period appears to be an important pathophysiological factor related to ventilation-perfusion abnormalities. Single photon emission computed tomography provides valuable clinical information for patient follow-up.

Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model.

Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients that is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents, corticosteroids (CS), and sepsis for 5 days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after 5 days' exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to 5 days' exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle-specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements, and sarcomeric proteins underlying the relative sparing of cranial vs. spinal nerve innervated muscles during exposure to the ICU intervention.

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.

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.

Inhalation anesthesia increases V/Q regional heterogeneity during spontaneous breathing in healthy subjects.

BACKGROUND: The underlying mechanism for the increased alveolar-arterial oxygen tension difference resulting from almost all forms of general anesthesia is unknown. We hypothesized that inhalation anesthesia influences the intrapulmonary distribution of ventilation (V) and perfusion (Q), leading to less advantageous V/Q matching. METHODS: Ten healthy volunteers were studied in supine position on two separate occasions, once awake and once during mild anesthesia (sevoflurane inhalation) with maintained spontaneous breathing. On both occasions, the distribution of V and Q were simultaneously imaged using single photon emission computed tomography. V was tagged with [Tc]-labeled carbon particle aerosol and Q with [In]-labeled macroaggregates of human albumin. Atelectasis formation during anesthesia was prevented using low concentrations of oxygen in inhaled air. RESULTS: Mean V and Q distributions in the ventral-to-dorsal direction, measured in 20 equally spaced volumes of interest and in three regions of interest of equal volume, did not differ between conditions. Anesthesia, when compared with the awake state, significantly decreased the total heterogeneity of the Q distribution (P = 0.002, effect size 1.16) but did not alter V (P = 0.37, effect size 0.41). The corresponding V/Q total heterogeneity was higher under anesthesia (P = 0.002, effect size 2.64). Compared to the awake state, the V/Q frequency distribution under anesthesia became wider (P = 0.009, 1.76 effect size) with a tendency toward low V/Q ratios. CONCLUSION: Inhalation anesthesia alone affects Q but not V, suggesting that anesthesia has a direct effect on the active regulatory mechanism coordinating Q with V, leading to less favorable V/Q matching.

Lung ventilation and perfusion in prone and supine postures with reference to anesthetized and mechanically ventilated healthy volunteers.

BACKGROUND: The literature on ventilation (V) and lung perfusion (Q) distributions during general anesthesia and controlled mechanical ventilation in supine and prone position is contradictory. The authors aimed to investigate whether V, Q, and ventilation to perfusion ratio (V/Q ratio) matching in anesthetized and mechanically ventilated volunteers are gravity dependent irrespective of posture. METHODS: Seven healthy volunteers were studied at two different occasions during general anesthesia and controlled mechanical ventilation. One occasion studied ventral to dorsal V and Q distributions in the supine posture and the other in the prone posture. Imaging was performed in supine posture at both occasions. A dual radiotracer technique and single photon emission computed tomography were used. V and Q were simultaneously tagged with Tc-Technegas (Tetley Manufacturing Ltd., Sydney, Australia) and In-labeled macroaggregates of human albumin (TechneScan LyoMAA, Mallinckrodt Medica, Petten, The Netherlands), respectively. RESULTS: No differences in V between postures were observed. Q differed between postures, being more uniform over different lung regions in prone posture and dependent in supine posture. The contribution of the vertical direction to the total V/Q ratio heterogeneity was larger in supine (31.4%) than in prone (16.4%) (P = 0.0639, two-tailed, paired t test) posture. CONCLUSIONS: During mechanical ventilation, prone posture favors a more evenly distributed Q between lung regions. V distribution is independent of posture. This results in a tendency toward lower V/Q gradients in the ventral to dorsal direction in prone compared with supine posture.

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.