[Preventing Crying after Revascularization Surgery in Pediatric Patients with Moyamoya Disease:Sedation with Dexmedetomidine].

BACKGROUND: Hyperventilation is a well-known risk factor of ischemic events in pediatric patients with moyamoya disease. For young children, it is important to avoid crying to prevent ischemic events because of their unstable postoperative hemodynamics. To prevent crying in pediatric patients, we used dexmedetomidine(DEX)for sedation immediately after revascularization surgery. OBJECTIVE: We investigated the effects of postoperative DEX use on hemodynamic changes and the avoidance of crying and hypocapnia in pediatric patients with moyamoya disease. CASE: Ten consecutive patients(5 boys and 5 girls)who underwent surgical revascularization were enrolled, and 16 hemispheres(8 boys and 8 girls)were sedated with DEX postoperatively between August 2011 and August 2016. METHODS: During extubation after revascularization, DEX was started at 0.4µg/kg/hr under spontaneous breathing and its dose was increased depending on the degree of consciousness, to maintain sedation of at least 3 on the Ramsay scale. DEX administration was terminated the next morning. RESULTS: Sedation was maintained well in all patients without hypocapnia, and no ischemic complications were observed. One patient cried and needed additional intravenous DEX injections and was immediately re-sedated;no hypocapnia developed. Respiratory depression did not occur and changes in respiratory rate and decreases in SpO2 were not observed. No significant changes in systolic blood pressure and heart rate were observed. CONCLUSION: Dexmedetomidine is safe and useful for postoperative sedation in children with moyamoya disease.

Purinergic and adenosine receptors contribute to hypoxic hyperventilation in zebrafish (Danio rerio).

The chemoreceptors involved in oxygen sensing in teleost fish are neuroepithelial cells (NECs) in the gills, and are analogous to glomus cells in the mammalian carotid body. Purinergic signalling mechanisms involving the neurotransmitters, ATP and adenosine, have been identified in mediating hypoxic signalling in the carotid body, but these pathways are not well understood in the fish gill. The present study used a behavioural assay to screen for the effects of drugs, that target purinergic and adenosine receptors, on the hyperventilatory response to hypoxia in larval zebrafish (Danio rerio) in order to determine if the receptors on which these drugs act may be involved in hypoxic signalling. The purinergic receptor antagonist, PPADS, targets purinergic P2X2/3 receptors and inhibited the hyperventilatory response to hypoxia (IC50=18.9µM). The broad-spectrum purinergic agonist, ATPγS, elicited a hyperventilatory response (EC50=168µM). The non-specific adenosine receptor antagonist, caffeine, inhibited the hyperventilatory response to hypoxia, as did the specific A2a receptor antagonist, SCH58261 (IC50=220nM). These results suggest that P2X2/3 and A2a receptors are candidates for mediating hypoxic hyperventilation in zebrafish. This study highlights the potential of applying chemical screening to ventilatory behaviour in zebrafish to further our understanding of the pathways involved in signalling by gill NECs and oxygen sensing in vertebrates.

Feasibility of the capnogram to monitor ventilation rate during cardiopulmonary resuscitation.

AIM: The rates of chest compressions (CCs) and ventilations are both important metrics to monitor the quality of cardiopulmonary resuscitation (CPR). Capnography permits monitoring ventilation, but the CCs provided during CPR corrupt the capnogram and compromise the accuracy of automatic ventilation detectors. The aim of this study was to evaluate the feasibility of an automatic algorithm based on the capnogram to detect ventilations and provide feedback on ventilation rate during CPR, specifically addressing intervals where CCs are delivered. METHODS: The dataset used to develop and test the algorithm contained in-hospital and out-of-hospital cardiac arrest episodes. The method relies on adaptive thresholding to detect ventilations in the first derivative of the capnogram. The performance of the detector was reported in terms of sensitivity (SE) and Positive Predictive Value (PPV). The overall performance was reported in terms of the rate error and errors in the hyperventilation alarms. Results were given separately for the intervals with CCs. RESULTS: A total of 83 episodes were considered, resulting in 4880min and 46,740 ventilations (8741 during CCs). The method showed an overall SE/PPV above 99% and 97% respectively, even in intervals with CCs. The error for the ventilation rate was below 1.8min-1 in any group, and >99% of the ventilation alarms were correctly detected. CONCLUSION: A method to provide accurate feedback on ventilation rate using only the capnogram is proposed. Its accuracy was proven even in intervals where canpography signal was severely corrupted by CCs. This algorithm could be integrated into monitor/defibrillators to provide reliable feedback on ventilation rate during CPR.

Real-time tidal volume feedback guides optimal ventilation during simulated CPR.

PURPOSE: We performed this study to investigate whether real-time tidal volume feedback increases optimal ventilation and decreases hyperventilation during manikin-simulated cardiopulmonary resuscitation (CPR). BASIC PROCEDURES: We developed a new real-time tidal volume monitoring device (TVD) which estimated tidal volume in real time using a magnetic flowmeter. The TVD was validated with a volume-controlled mechanical ventilator with various tidal volumes. We conducted a randomized, crossover, manikin-simulation study in which 14 participants were randomly divided into a control (without tidal volume feedback, n = 7) and a TVD group (with real-time tidal volume feedback, n = 7) and underwent manikin simulation. The optimal ventilation was defined as 420-490 mL of tidal volumes for a 70-kg adult manikin. After 2 weeks of the washout period, the simulation was repeated via the participants' crossover. MAIN FINDINGS: In the validation study, 97.6% and 100% of the difference ratios in tidal volumes between the mechanical ventilator and TVD were within ±1.5% and ±2.5%, respectively. During manikin-simulated CPR, TVD use increased the proportion of optimal ventilation per person. Its median values (range) of the control group and the TVD group were 37.5% (0.0-65.0) and 87.5% (65.0-100.0), respectively, P < .001). TVD use also decreased hyperventilation. The proportions of hyperventilation in the control group and the TVD group were 25.0% vs 8.9%, respectively (P < .001). PRINCIPAL CONCLUSIONS: Real-time tidal volume feedback using the new TVD guided the rescuers to provide optimal ventilation and to avoid hyperventilation during manikin-simulated CPR.

Evaluation of Bag-Valve-Mask Ventilation in Manikin Studies: What Are the Current Limitations?

Introduction. Manikin-based studies for evaluation of ventilation performance show high heterogeneity in the analysis and experimental methods used as we pointed out in previous studies. In this work, we aim to evaluate these potential limitations and propose a new analysis methodology to reliably assess ventilation performance. Methods. One hundred forty healthcare providers were selected to ventilate a manikin with two adult self-inflating bags in random order. Ventilation parameters were analysed using different published analysis methods compared to ours. Results. Using different methods impacts the evaluation of ventilation efficiency which ranges from 0% to 45.71%. Our new method proved relevant and showed that all professionals tend to cause hyperventilation and revealed a significant relationship between professional category, grip strength of the hand keeping the mask, and ventilation performance (p = 0.0049 and p = 0.0297, resp.). Conclusion. Using adequate analysis methods is crucial to avoid many biases. Extrapolations to humans still have to be taken with caution as many factors impact the evaluation of ventilation performance. Healthcare professionals tend to cause hyperventilation with current devices. We believe this problem could be prevented by implementing monitoring tools in order to give direct feedback to healthcare professionals regarding ventilation efficiency and ventilatory parameter values.

[Long-term dental interventions in mentally retarded children under general anesthesia with sevoflurane].

Dental procedures in mentally retarded children is challenging for both dentist and for anesthesiologist. The aim of the study was to evaluate the efficacy and safety of dental care procedures under general anesthesia with sevoflurane by means of laryngeal mask in mentally retarded children. The randomized controlled study included 65 mentally retarded children with ASA 2-3 who underwent dental treatment. All patients had multiple caries. The children were divided into two groups. The first group included 35 children with normal body weigh while the second one - 30 obese children. All patients received a rapid induction with sevoflurane with the subsequent installation of the laryngeal mask. In the second group the signs of hypoventilation recorded an average of 10 ± 4 minutes after induction of anesthesia, which was manifested in increasing Pсо2greater than 50 mm Hg. In the first group, the signs of hypoventilation marked an average of 18 ± 3.5 minutes from the start of induction of anesthesia. All patients were transferred to the artificial lung ventilation through the LMA. By dental treatment under general anesthesia with sevoflurane and laryngeal mask all mentally retarded children had respiratory depression with increased levels of carbon dioxide greater than 50 mmHg, but obese children developed these signs of hypoventilation twice as fast. Conducting long dental treatment in mentally retarded children require artificial lung ventilation.

Voluntary suppression of hyperthermia-induced hyperventilation mitigates the reduction in cerebral blood flow velocity during exercise in the heat.

Hyperthermia during prolonged exercise leads to hyperventilation, which can reduce arterial CO2 pressure (PaCO2 ) and, in turn, cerebral blood flow (CBF) and thermoregulatory response. We investigated 1) whether humans can voluntarily suppress hyperthermic hyperventilation during prolonged exercise and 2) the effects of voluntary breathing control on PaCO2 , CBF, sweating, and skin blood flow. Twelve male subjects performed two exercise trials at 50% of peak oxygen uptake in the heat (37°C, 50% relative humidity) for up to 60 min. Throughout the exercise, subjects breathed normally (normal-breathing trial) or they tried to control their minute ventilation (respiratory frequency was timed with a metronome, and target tidal volumes were displayed on a monitor) to the level reached after 5 min of exercise (controlled-breathing trial). Plotting ventilatory and cerebrovascular responses against esophageal temperature (Tes) showed that minute ventilation increased linearly with rising Tes during normal breathing, whereas controlled breathing attenuated the increased ventilation (increase in minute ventilation from the onset of controlled breathing: 7.4 vs. 1.6 l/min at +1.1°C Tes; P < 0.001). Normal breathing led to decreases in estimated PaCO2 and middle cerebral artery blood flow velocity (MCAV) with rising Tes, but controlled breathing attenuated those reductions (estimated PaCO2 -3.4 vs. -0.8 mmHg; MCAV -10.4 vs. -3.9 cm/s at +1.1°C Tes; P = 0.002 and 0.011, respectively). Controlled breathing had no significant effect on chest sweating or forearm vascular conductance (P = 0.67 and 0.91, respectively). Our results indicate that humans can voluntarily suppress hyperthermic hyperventilation during prolonged exercise, and this suppression mitigates changes in PaCO2 and CBF.

Inhibition of peripheral dopamine metabolism and the ventilatory response to hypoxia in the rat.

Dopamine (DA) is a putative neurotransmitter in the carotid body engaged in the generation of the hypoxic ventilatory response (HVR). However, the action of endogenous DA is unsettled. This study seeks to determine the ventilatory effects of increased availability of endogenous DA caused by inhibition of DA enzymatic breakdown. The peripheral inhibitor of MAO - debrisoquine, or COMT - entacapone, or both combined were injected to conscious rats. Ventilation and its responses to acute 8 % O(2) in N(2) were investigated in a whole body plethysmograph. We found that inhibition of MAO augmented the hyperventilatory response to hypoxia. Inhibition of COMT failed to influence the hypoxic response. However, simultaneous inhibition of both enzymes, the case in which endogenous availability of DA should increase the most, reversed the hypoxic augmentation of ventilation induced by MAO-inhibition. The inference is that when MAO alone is blocked, COMT takes over DA degradation in a compensatory way, which lowers the availability of DA, resulting in a higher intensity of the HVR. We conclude that MAO is the enzyme predominantly engaged in the chemoventilatory effects of DA. Furthermore, the findings imply that endogenous DA is inhibitory, rather than stimulatory, for hypoxic ventilation.

[Calpains: general characteristics and role in various states of the organism].

Calpains are a family of cytoplasmic calcium-dependent proteinases with papain-like activity. They participate in a variety of processes in the body: age changes, functioning of endothelium and pulmonary system, regulation of apoptosis and necrosis, development of various hypometabolic states, arterial hypertension, diabetes and chronic kidney disease, tumor growth. It is concluded that calpains, causing limited proteolysis of substrates, play an important role in a wide range of biological phenomena. Their activity is associated with the response to the calcium-dependent signaling and the effects of aging. Inhibition of calpains activity contributes to inhibition of endothelial dysfunction, cardiovascular disease, formation of structural and functional changes in the kidney tissue, has neuroprotective effect, preventing sarcopenia, reduces inflammatory reactions caused by hyperventilation of the lungs.

Ferric Iron and Cobalt (III) compounds to safely decrease hydrogen sulfide in the body?

To sort out the putative roles of endogenous hydrogen sulfide (H2S) in clinical conditions wherein systemic inflammation or hypoxia is present, it becomes crucial to develop approaches capable of affecting H2S concentration that can be safely applied in humans. We have investigated a paradigm, which could achieve such a goal, using vitamin B12 (vit.B12), at the dose recommended in cyanide poisoning, and very low levels of methemoglobin (MetHb). Hydroxocobalamin in the plasma, supernatant of kidney, and heart tissue homogenates of rats that had received vit.B12 (140 mg.kg(-1) intravenous) was found in the µM range. Exogenous H2S (100 µM) added to the plasma or supernatants of these rats decreased at a significantly higher rate than in control rats. In the latter however a spontaneous oxidation of exogenous H2S occurred. In vitro, hydroxocobalamin solution (100 µM) decreased, within <2 min, an equimolar concentration of H2S by 80%. Three to five percent MetHb prevented H2S induced hyperventilation in vivo and decreased exogenous H2S in vitro by 25-40 µM within 30 s. Our observations lead to the hypothesis that innocuous levels of MetHb and vit.B12 could be a used as an effective and safe way to test the role of endogenous H2S in vivo.

Effects of socio-emotional stressors on ventilation rate and subjective workload during simulated CPR by lay rescuers.

Several studies have documented the occurrence of high ventilation rates during cardiopulmonary resuscitation, but to date, there have been no scientific investigation of the causes of hyperventilation. The objective of the current study was to test the effects of socio-emotional stressors on lay rescuers' ventilation rate in a simulated resuscitation setting using a manikin model. A within-subjects experiment with randomized order of conditions tested lay rescuers' ventilation rate on an intubated manikin during exposure to socio-emotional stressors and during a control condition where no external stressors were present. Ventilation rates and subjective workload were significantly higher during exposure to socio-emotional stressors than during the control condition. All but one of the nine participants ventilated at a higher ventilation rate in the experimental condition. All nine participants rated the subjective workload to be higher during exposure to socio-emotional stressors. Hence, exposure to socio-emotional stressors is associated with increased ventilation rates performed by lay rescuers during simulated cardiac arrest using a manikin model. These findings might have implications for the understanding of the type of situations which hyperventilation may occur. Awareness of these situations may have implications for training of lay rescues.

Hyperventilation in pediatric resuscitation: performance in simulated pediatric medical emergencies.

OBJECTIVE: To examine the hypothesis that pediatric resuscitation providers hyperventilate patients via bag-valve-mask (BVM) ventilation during performance of cardiopulmonary resuscitation (CPR), quantify the degree of excessive ventilation provided, and determine if this tendency varies according to provider type. METHODS: A retrospective, observational study was conducted of 72 unannounced, monthly simulated pediatric medical emergencies ("mock codes") in a tertiary care, academic pediatric hospital. Responders were code team members, including pediatric residents and interns (MDs), respiratory therapists (RTs), and nurses (RNs). All sessions were video-recorded and reviewed for the rate of BVM ventilation, rate of chest compressions, and the team members performing these tasks. The type of emergency, location of the code, and training level of the team leader were also recorded. RESULTS: Hyperventilation was present in every mock code reviewed. The mean rate of BVM ventilation for all providers in all scenarios was 40.6 ± 11.8 breaths per minute (BPM). The mean ventilation rates for RNs, RTs, and MDs were 40.8 ± 14.7, 39.9 ± 11.7, and 40.5 ± 10.3 BPM, respectively, and did not differ among providers (P = .94). All rates were significantly higher than the recommended rate of 8 to 20 BPM (per Pediatric Advanced Life Support guidelines, varies with patient age) (P < .001). The mean ventilation rate in cases of isolated respiratory arrest was 44.0 ± 13.9 BPM and was not different from the mean BVM ventilation rate in cases of cardiopulmonary arrest (38.9 ± 14.4 BPM; P = .689). CONCLUSIONS: Hyperventilation occurred in simulated pediatric resuscitation and did not vary according to provider type. Future educational interventions should focus on avoidance of excessive ventilation.

Capnography and chest-wall impedance algorithms for ventilation detection during cardiopulmonary resuscitation.

OBJECTIVE: Hyperventilation is both common and detrimental during cardiopulmonary resuscitation (CPR). Chest-wall impedance algorithms have been developed to detect ventilations during CPR. However, impedance signals are challenged by noise artifact from multiple sources, including chest compressions. Capnography has been proposed as an alternate method to measure ventilations. We sought to assess and compare the adequacy of these two approaches. METHODS: Continuous chest-wall impedance and capnography were recorded during consecutive in-hospital cardiac arrests. Algorithms utilizing each of these data sources were compared to a manually determined "gold standard" reference ventilation rate. In addition, a combination algorithm, which utilized the highest of the impedance or capnography values in any given minute, was similarly evaluated. RESULTS: Data were collected from 37 cardiac arrests, yielding 438min of data with continuous chest compressions and concurrent recording of impedance and capnography. The manually calculated mean ventilation rate was 13.3+/-4.3/min. In comparison, the defibrillator's impedance-based algorithm yielded an average rate of 11.3+/-4.4/min (p=0.0001) while the capnography rate was 11.7+/-3.7/min (p=0.0009). There was no significant difference in sensitivity and positive predictive value between the two methods. The combination algorithm rate was 12.4+/-3.5/min (p=0.02), which yielded the highest fraction of minutes with respiratory rates within 2/min of the reference. The impedance signal was uninterpretable 19.5% of the time, compared with 9.7% for capnography. However, the signals were only simultaneously non-interpretable 0.8% of the time. CONCLUSIONS: Both the impedance and capnography-based algorithms underestimated the ventilation rate. Reliable ventilation rate determination may require a novel combination of multiple algorithms during resuscitation.

Comparison of a 10-breaths-per-minute versus a 2-breaths-per-minute strategy during cardiopulmonary resuscitation in a porcine model of cardiac arrest.

BACKGROUND: Hyperventilation during cardiopulmonary resuscitation (CPR) is harmful. METHODS: We tested the hypotheses that, during CPR, 2 breaths/min would result in higher cerebral perfusion pressure and brain-tissue oxygen tension than 10 breaths/min, and an impedance threshold device (known to increase circulation) would further enhance cerebral perfusion and brain-tissue oxygen tension, especially with 2 breaths/min. RESULTS: Female pigs (30.4 +/- 1.3 kg) anesthetized with propofol were subjected to 6 min of untreated ventricular fibrillation, followed by 5 min of CPR (100 compressions/min, compression depth of 25% of the anterior-posterior chest diameter), and ventilated with either 10 breaths/min or 2 breaths/min, while receiving 100% oxygen and a tidal volume of 12 mL/kg. Brain-tissue oxygen tension was measured with a probe in the parietal lobe. The impedance threshold device was then used during an 5 additional min of CPR. During CPR the mean +/- SD calculated coronary and cerebral perfusion pressures with 10 breaths/min versus 2 breaths/min, respectively, were 17.6 +/- 9.3 mm Hg versus 14.3 +/- 6.5 mm Hg (p = 0.20) and 16.0 +/- 9.5 mm Hg versus 9.3 +/- 12.5 mm Hg (p = 0.25). Carotid artery blood flow, which was prospectively designated as the primary end point, was 65.0 +/- 49.6 mL/min in the 10-breaths/min group, versus 34.0 +/- 17.1 mL/min in the 2-breaths/min group (p = 0.037). Brain-tissue oxygen tension was 3.0 +/- 3.3 mm Hg in the 10-breaths/min group, versus 0.5 +/- 0.5 mm Hg in the 2-breaths/min group (p = 0.036). After 5 min of CPR there were no significant differences in arterial pH, PO2, or PCO2 between the groups. During CPR with the impedance threshold device, the mean carotid blood flow and brain-tissue oxygen tension in the 10-breaths/min group and the 2-breaths/min group, respectively, were 102.5 +/- 67.9 mm Hg versus 38.8 +/- 23.7 mm Hg (p = 0.006) and 4.5 +/- 6.0 mm Hg versus 0.7 +/- 0.7 mm Hg (p = 0.032). CONCLUSIONS: Contrary to our initial hypothesis, during the first 5 min of CPR, 2 breaths/min resulted in significantly lower carotid blood flow and brain-tissue oxygen tension than did 10 breaths/min. Subsequent addition of an impedance threshold device significantly enhanced carotid flow and brain-tissue oxygen tension, especially in the 10-breaths/min group.

Paramedic intubation of patients with severe head injury: a review of current Australian practice and recommendations for change.

Secondary brain injury may occur early after severe traumatic brain injury due to hypoxia and/or hypotension. Prehospital care by ambulance paramedics has the goal of preventing and treating these complications and, thus, improving outcomes. In Australia, most ambulance services recommend paramedics attempt endotracheal intubation in patients with severe head injury. Even though most patients with severe head injury retain airway reflexes, most states do not allow the use of appropriate drugs to facilitate intubation. In contrast, recent evidence from trauma registries suggests that this approach may be associated with significantly worse outcomes compared with no intubation. Two states allow intubation facilitated by sedative (but not relaxant) drugs, but this has a low success rate and could worsen brain injury because of a decrease in cerebral perfusion pressure. For road-based paramedics, the role of rapid sequence intubation is uncertain. Given the risks of this procedure and the lack of proven benefit, this procedure should not be introduced without supportive evidence from randomised, controlled trials. In contrast, for safety reasons, comatose patients transported by helicopter should undergo rapid sequence intubation prior to flight. However, this is not authorised in most states, despite good supportive evidence that this can be safely and effectively undertaken by paramedics. Finally, there is evidence that inadvertent hyperventilation is associated with adverse outcome, yet only two ambulance services use waveform capnography in head injury patients who are intubated. Overall, current paramedic airway practice in most states of Australia is not supported by the evidence and is probably associated with worse patient outcomes after severe head injury. For road-based paramedics, rapid transport to hospital without intubation should be regarded as the current standard of care. Rapid sequence intubation should be limited to use within appropriate clinical trials, or patients transported by helicopter. For patients who are intubated, waveform capnography is essential to confirm tracheal placement and to prevent inadvertent hyperventilation.

Optimizing the intraoperative management of carbon dioxide concentration.

PURPOSE OF REVIEW: This review assesses whether there is a carbon dioxide concentration range that provides optimum benefit to the patient intraoperatively. It includes the physiological effects of carbon dioxide on various organ systems in awake and anesthetized individuals and its clinical effects in the ischemia/reperfusion setting. This review will present views on end-tidal or arterial carbon dioxide tension management in the perioperative period. RECENT FINDINGS: Hypocapnia reduces intracranial pressure and is used by clinicians during acute traumatic brain injury, acute intracranial hemorrhage, and acutely growing brain tumors. There is mounting evidence, however, that hypercapnia improves tissue perfusion and oxygenation. Therefore, clinicians may want to induce mild-to-moderate hypercapnia during reperfusion states such as major vascular surgery, organ transplantation, tissue-graft surgery, and cases managed with low mean arterial pressures to control bleeding. As hypercapnia preserves cerebral blood flow even under relatively low perfusion pressures, it may be beneficial during global reperfusion scenarios. This hypothesis needs to be tested extensively before being considered for clinical applications. From a different perspective, current American Heart Association Guidelines recommend 12-15 breaths/min during cardiopulmonary resuscitation and stress the potential negative role of inadvertent hyperventilation on survival outcome. The importance of this concept is discussed briefly. SUMMARY: Overall, the benefits of managing carbon dioxide concentration intraoperatively for the maintenance of cardiac output, tissue oxygenation, perfusion, intracranial pressure, and cerebrovascular reactivity are well defined.