Are we there yet? A critical evaluation of sudden and unexpected death in epilepsy models.

Although animal models have helped to elaborate meaningful hypotheses about the pathophysiology of sudden and unexpected death in epilepsy (SUDEP), specific prevention strategies are still lacking, potentially reflecting the limitations of these models and the intrinsic difficulties of investigating SUDEP. The interpretation of preclinical data and their translation to diagnostic and therapeutic developments in patients thus require a high level of confidence in their relevance to model the human situation. Preclinical models of SUDEP are heterogeneous and include rodent and nonrodent species. A critical aspect is whether the animals have isolated seizures exclusively induced by a specific trigger, such as models where seizures are elicited by electrical stimulation, pharmacological intervention, or DBA mouse strains, or whether they suffer from epilepsy with spontaneous seizures, with or without spontaneous SUDEP, either of nongenetic epilepsy etiology or from genetically based developmental and epileptic encephalopathies. All these models have advantages and potential disadvantages, but it is important to be aware of these limitations to interpret data appropriately in a translational perspective. The majority of models with spontaneous seizures are of a genetic basis, whereas SUDEP cases with a genetic basis represent only a small proportion of the total number. In almost all models, cardiorespiratory arrest occurs during the course of the seizure, contrary to that in patients observed at the time of death, potentially raising the issue of whether we are studying models of SUDEP or models of periseizure death. However, some of these limitations are impossible to avoid and can in part be dependent on specific features of SUDEP, which may be difficult to model. Several preclinical tools are available to address certain gaps in SUDEP pathophysiology, which can be used to further validate current preclinical models.

Effect of adenosinergic manipulations on amygdala-kindled seizures in mice: Implications for sudden unexpected death in epilepsy.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) results in more years of potential life lost than any neurological condition with the exception of stroke. It is generally agreed that SUDEP happens due to some form of respiratory, cardiac, and electrocerebral dysfunction following a seizure; however, the mechanistic cause of these perturbations is unclear. One possible explanation lies with adenosinergic signaling. Extracellular levels of the inhibitory neuromodulator adenosine rapidly rise during seizures, a countermeasure that is necessary for seizure termination. Previous evidence has suggested that excessive adenosinergic inhibition could increase the risk of SUDEP by silencing brain areas necessary for life, such as the respiratory nuclei of the brainstem. The goal of this investigation was to further clarify the role of adenosine in seizure-induced respiratory and electrocerebral dysfunction. METHODS: To determine the role of adenosine in postictal physiological dysregulation, we pharmacologically manipulated adenosine signaling prior to amygdala-kindled seizures in mice while recording electroencephalogram (EEG), electromyogram, and breathing using whole body plethysmography. The adenosinergic drugs used in this study included selective and nonselective adenosine receptor antagonists and inhibitors of adenosine metabolism. RESULTS: We found that high doses of adenosine receptor antagonists caused some seizures to result in seizure-induced death; however, counterintuitively, animals in these conditions that did not experience seizure-induced death had little or no postictal generalized EEG suppression. Inhibitors of adenosine metabolism had no effect on postictal breathing but did worsen some postictal electrocerebral outcomes. SIGNIFICANCE: The unexpected effect of high doses of adenosine antagonists on seizure-induced death observed in this study may be due to the increase in seizure severity, vasoconstriction, or phosphodiesterase inhibition caused by these drugs at high doses. These findings further clarify the role of adenosine in seizure-induced death and may have implications for the consumption of caffeine in epilepsy patients and the prevention of SUDEP.

Evaluation of propofol-based procedural sedation in pediatric hemato-oncological patients provided by physician assistants in anesthesia.

BACKGROUND: Procedural sedation and analgesia are required for painful hemato-oncological procedures such as lumbar and bone marrow punctures. At our institution, sedation with propofol and alfentanil is usually provided by Physician Assistants in Anesthesia. We evaluated the adverse events during the PSA program for children, provided by Physician Assistants in Anesthesia. PATIENTS AND METHODS: We included pediatric patients meeting our criteria for deep sedation by a Physician Assistants in Anesthesia, scheduled for a hemato-oncological procedure at the Amalia Children's Hospital at the Radboudumc Nijmegen. The primary outcome was oxygen desaturation below 92% for more than 20 s. We prospectively collected data on demographics, current health problems, type of procedure, need for airway interventions, and hypotension. RESULTS: We collected data from 437 sedation sessions involving 71 patients. No oxygen desaturation below 92% lasting longer than 20 s occurred. In 2 cases, a jaw thrust was performed. No invasive airway techniques (oropharyngeal cannula, laryngeal mask, or intubation) were required. A significant drop in mean arterial pressure was seen in 2 out of 437 cases (0.5%). There was no occurrence of cardiopulmonary resuscitation or other adverse events such as aspiration or laryngeal spasm. CONCLUSIONS: Sedation and analgesia for short painful procedures in selected pediatric hemato-oncological units with a dedicated protocol may be safely provided by trained and certified Physician Assistants in Anesthesia.

Comparative Study of Terminal Cortical Potentials Using Iridium and Ag/AgCl Electrodes.

Brain ischemia induces slow voltage shifts in the cerebral cortex, including waves of spreading depolarization (SD) and negative ultraslow potentials (NUPs), which are considered as brain injury markers. However, different electrode materials and locations yield variable SD and NUP features. Here, we compared terminal cortical events during isoflurane or sevoflurane euthanasia using intracortical linear iridium electrode arrays and Ag/AgCl-based electrodes in the rat somatosensory cortex. Inhalation of anesthetics caused respiratory arrest, associated with hyperpolarization and followed by SD and NUP on both Ir and Ag electrodes. Ag-NUPs were bell shaped and waned within half an hour after death. Ir-NUPs were biphasic, with the early fast phase corresponding to Ag-NUP, and the late absent on Ag electrodes, phase of a progressive depolarizing voltage shift reaching -100 mV by two hours after death. In addition, late Ir-NUPs were more ample in the deep layers than at the cortical surface. Thus, intracortical Ag and Ir electrodes reliably assess early manifestations of terminal brain injury including hyperpolarization, SD and the early phase of NUP, while the late, giant amplitude phase of NUP, which is present only on Ir electrodes, is probably related to the sensitivity of Ir electrodes to a yet unidentified factor related to brain death.

Update on ventilation management in the Pediatric Intensive Care Unit.

Studies have shown that up to 63% of pediatric intensive care unit patients admitted with acute respiratory or cardiorespiratory illness require mechanical ventilation. Mechanical ventilator support can be divided into three phases: initiation, escalation, and resolution. Noninvasive ventilation is typical during the initiation phase in the management of acute pediatric respiratory failure. The major advancements in the use of noninvasive ventilation involve the emergence of high-flow nasal cannula and how widespread the use of high-flow nasal cannula has become in pediatric critical care practice. When high-flow nasal cannula fails, escalation to continuous positive airway pressure or bi-level positive airway pressure is the next step in respiratory care progression. Careful clinical assessment is necessary to avoid delayed escalation between forms of noninvasive support or escalation to intubation and invasive mechanical ventilation. Advancements in conventional mechanical ventilation are centered on optimizing ventilator settings and customizing monitoring with the overarching goal to reduce complications of mechanical ventilation, such as ventilator-induced lung injury. New mechanical ventilator strategies integrating esophageal pressure monitoring, volumetric capnography, and neurally adjusted ventilator assist help to optimize conventional ventilator support. Nonconventional modes of ventilation in the intensive care unit are high-frequency modes and airway pressure release ventilation. Extracorporeal pulmonary support via extracorporeal membrane oxygenation or paracorporeal lung assist devices provides rescue options when conventional and nonconventional methods fail. During resolution of a course of mechanical ventilator support, reliable weaning strategies and extubation readiness testing are lacking in pediatric critical care. Further, timing of tracheostomy, risk reduction in ventilator-induced lung injury, and decreased sedation requirements in pediatric patients requiring mechanical ventilation in the pediatric intensive care unit are areas of ongoing research.

Comparison between automated cardiopulmonary resuscitation and manual cardiopulmonary resuscitation in the rescue of cardiac and respiratory arrest.

Objective: To compare the efficacy of automated cardiopulmonary resuscitation (A-CPR) and manual cardiopulmonary resuscitation (M-CPR) in the rescue of cardiac and respiratory arrest. Methods: A retrospective, single-center observational study was conducted to identify 106 patients by reviewing medical records of 269 patients with cardiac and respiratory arrest treated in The Second Hospital of Hebei Medical University, Shandong Provincial Third Hospital (Jinan, China) from February 2019 to February 2021. Patients were divided into A-CPR group (n = 55) and M-CPR group (n = 51) based on the resuscitation treatment method. The groups were matched for age, gender and the cause of cardiac arrest. Rescue effects, blood gas analysis indicators, respiratory dynamics and condition improvement of the two groups were compared. Results: In terms of rescue effects, return of spontaneous circulation (ROSC) rate, successful rate of cardiopulmonary resuscitation (CPR), 24-hour survival rate and survival discharge rate in the A-CPR group were higher than M-CPR group (P<0.05). With respect to blood gas analysis indicators and respiratory dynamics, the partial pressure of carbon dioxide (PaCO2) in the A-CPR group was lower than M-CPR group at 15 and 30 minutes after CPR, while the partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), end expiratory carbon dioxide (PetCO2), coronary perfusion pressure (CPP) and mean arterial pressure (MAP) in the A-CPR group were higher than M-CPR group (P<0.05). In aspect of condition improvement, spontaneous breathing, heart rate, spontaneous circulation, blood pressure recovery time and CPR time in the A-CPR group were shorter than M-CPR group (P<0.05). Conclusion: The application effect of A-CPR in the rescue of cardiac and respiratory arrest, the improvement of blood gas analysis indexes, respiration and condition improvement are more significant than M-CPR.

Thrombin action on astrocytes in the hindbrain of the rat disrupts glycemic and respiratory control.

Severe trauma can produce a postinjury "metabolic self-destruction" characterized by catabolic metabolism and hyperglycemia. The severity of the hyperglycemia is highly correlated with posttrauma morbidity and mortality. Although no mechanism has been posited to connect severe trauma with a loss of autonomic control over metabolism, traumatic injury causes other failures of autonomic function, notably, gastric stasis and ulceration ("Cushing's ulcer"), which has been connected with the generation of thrombin. Our previous studies established that proteinase-activated receptors (PAR1; "thrombin receptors") located on astrocytes in the autonomically critical nucleus of the solitary tract (NST) can modulate gastric control circuit neurons to cause gastric stasis. Hindbrain astrocytes have also been implicated as important detectors of low glucose or glucose utilization. When activated, these astrocytes communicate with hindbrain catecholamine neurons that, in turn, trigger counterregulatory responses (CRR). There may be a convergence between the effects of thrombin to derange hindbrain gastrointestinal control and the hindbrain circuitry that initiates CRR to increase glycemia in reaction to critical hypoglycemia. Our results suggest that thrombin acts within the NST to increase glycemia through an astrocyte-dependent mechanism. Blockade of purinergic gliotransmission pathways interrupted the effect of thrombin to increase glycemia. Our studies also revealed that thrombin, acting in the NST, produced a rapid, dramatic, and potentially lethal suppression of respiratory rhythm that was also a function of purinergic gliotransmission. These results suggest that the critical connection between traumatic injury and a general collapse of autonomic regulation involves thrombin action on astrocytes.

Seizures induce obstructive apnea in DBA/2J audiogenic seizure-prone mice: Lifesaving impact of tracheal implants.

The mechanism(s) for sudden death in epilepsy (SUDEP) remain(s) unknown, but seizure spread to brainstem areas serving autonomic and respiratory function is critical. In a rat model, we established a mechanism for SUDEP that involves seizure-induced laryngospasm and obstructive apnea lasting until respiratory arrest. We hypothesized that DBA/2J mice, which display lethal audiogenic seizures, would be protected from death by implanting a tracheal T-tube as a surrogate airway. In a 2 × 2 design, mice were implanted with either open or closed tracheal T-tubes and treated with either low-dose ketamine/xylazine to moderate thoracic spasm during the tonic seizure phase or no drug. Animals receiving both treatments had the highest survival rate, followed by animals receiving the open tube without ketamine/xylazine. The odds ratio for survival was >20 higher with an open T-tube (odds ratio = 24.14). The impact of open tracheal tubes indicates that the mechanism of death in DBA/2J mice involves seizure-induced upper airway obstruction until respiratory arrest. These results, our rat work, and our demonstration of inspiratory effort-based electromyographic signals and electrocardiographic abnormalities in rats and humans suggest that seizure-induced laryngospasm and obstructive apnea directly link seizure activity to respiratory arrest in these sudden death examples.

Population-Based Incidence of Potentially Life-Threatening Complications of Hypocalcemia and the Role of Vitamin D Deficiency.

OBJECTIVES: To determine the incidence of potentially life-threatening complications of hypocalcemia in infants and children in Olmsted County, Minnesota; and to determine if vitamin D deficiency contributed to these events and was, at the time of clinical presentation, considered as a possible cause. STUDY DESIGN: In this population-based descriptive study, data were abstracted from the Rochester Epidemiology Project, a medical record linkage system covering 95% of patients in Olmsted County, Minnesota. Participants were children aged 0-5 years who resided in Olmsted County between January 1, 1996 and June 30, 2017, and who received diagnoses of seizures, cardiomyopathy, cardiac arrest, respiratory arrest, laryngospasm, and/or tetany. The incidence of hypocalcemia plus a potentially life-threatening complication was calculated. RESULTS: Among 15 419 patients aged 0-5 years in Olmsted County during the study period, 1305 had eligible complications: 460 had serum calcium checked within 14 days of presentation and 85 had hypocalcemia. Patients were excluded when causes other than hypocalcemia likely triggered the complication, leaving 16 children whose complication was attributed to hypocalcemia. Three of these 16 patients had a serum 25-hydroxyvitamin D measurement and 2 were deficient (≤6 ng/mL [15 nmol/L]). Among children aged 0-5 years, the incidence of hypocalcemia plus a potentially life-threatening complication was 6.1 per 100 000 person-years (95% CI, 3.5-10.0). CONCLUSIONS: Vitamin D deficiency is an underinvestigated cause of complications of hypocalcemia in children. Serum calcium and 25-hydroxyvitamin D should be measured in children with these complications to identify possibly life-threatening vitamin D deficiency.

Neural activity in the periaqueductal gray and other specific subcortical structures is enhanced when a selective serotonin reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected death in epilepsy.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a critical issue in epilepsy, and DBA/1 mice are a useful animal model of this devastating epilepsy sequela. The serotonin hypothesis for SUDEP proposes that modifying serotonergic function significantly alters susceptibility to seizure-induced respiratory arrest (S-IRA). Agents that enhance serotonergic function, including a selective serotonin reuptake inhibitor, fluoxetine, selectively prevent S-IRA in DBA/1 mice. This study examined fluoxetine-induced changes in brain activity using manganese-enhanced magnetic resonance imaging (MEMRI) to reveal sites in the DBA/1 mouse brain where fluoxetine acts to prevent S-IRA. METHODS: DBA/1 mice were subjected to audiogenic seizures (Sz) after saline or fluoxetine (45 mg/kg, intraperitoneal) administration. Control DBA/1 mice received fluoxetine or saline, but Sz were not evoked. A previous MEMRI study established the regions of interest (ROIs) for Sz in the DBA/1 mouse brain, and the present study examined MEMRI differences in the ROIs of these mouse groups. RESULTS: The neural activity in several ROIs was significantly increased in fluoxetine-treated DBA/1 mice that exhibited Sz but not S-IRA when compared to the saline-treated mice that exhibited both Sz and respiratory arrest. These structures included the periaqueductal gray (PAG), amygdala, reticular formation (sensorimotor-limbic network), Kölliker-Fuse nucleus, facial-parafacial group (respiratory network), and pontine raphe. Of these ROIs, only the PAG showed significantly decreased neural activity with saline pretreatment when seizure-induced respiratory arrest occurred as compared to saline treatment without seizure. SIGNIFICANCE: The PAG is known to play an important compensatory role for respiratory distress caused by numerous exigent situations in normal animals. The pattern of fluoxetine-induced activity changes in the present study suggests that PAG may be the most critical target for fluoxetine's action to prevent seizure-induced sudden death. These findings have potential clinical importance, because there is evidence of anomalous serotonergic function and PAG imaging abnormalities in human SUDEP.

Acute respiratory failure secondary to a cervical goitre in a pregnant woman: a case report.

BACKGROUND: Pregnancy constitutes a significant factor in thyroid hypertrophy and can rarely progress to respiratory distress. We describe case of pregnant woman with acute respiratory distress following a tracheal compression due to goiter, quickly resulting in respiratory arrest, requiring emergency orotracheal intubation and thyroidectomy. CASE PRESENTATION: A pregnant woman with a growing goiter was referred to the hospital with a respiratory difficulty. During the examination, we found a large homogeneous goiter. The patient showed signs of respiratory exhaustion with bradypnea and pulmonary auscultation revealing decreased ventilation of the two pulmonary fields. The evolution quick led to respiratory arrest. The patient was rapidly intubated, which saved her. A thoracic computed tomography was performed and revealed a large goiter, compressing the trachea in its thoracic area and oppressing the vascular structures. Obstetrical ultrasound was normal. Thyroidectomy was decided after the patient's preparation. After 24 h, the patient was successfully extubated without incident and the postoperative period was uneventful. CONCLUSION: Airway obstruction during pregnancy secondary to goiter is rare but can be fatal. Early diagnosis might have avoided the evolution towards the respiratory failure. Prevention requires early surgery preferably before pregnancy or in our case a surgery in the second trimester.

Basic life support for the child and infant.

The majority of cardiorespiratory arrests in children and infants are caused by respiratory insufficiency rather than cardiac problems; therefore, the order of delivering resuscitation is different to the delivery of basic life support to adults. The Nursing and Midwifery Council has stated that all nurses must be able to provide basic life support. This article will explain the process for recognising the need for, and delivering, basic life support to infants and children.

The mechanisms of sudden-onset type adverse reactions to oseltamivir.

Oseltamivir is contraindicated for people aged 10-19 in principle in Japan, due to concern about abnormal behaviours. Sudden death is another concern. This review examines growing evidence of their association and discusses underlying mechanisms of these sudden-onset type reactions to oseltamivir. First, the importance of animal models and the concept of human equivalent dose (HED) is summarized. Second, the specific condition for oseltamivir use, influenza infection, is reviewed. Third, findings from toxicity studies conducted prior to and after the marketing of oseltamivir are reported on to provide context on the observation of a possible causal association. Fourth, similarity and consistency of toxicity in humans with that in other animals is described. Finally, coherence of toxicokinetic and molecular level of evidence (channels, receptors and enzymes), including differences from the toxicity of other neuraminidase inhibitors, is reviewed. It is concluded that unchanged oseltamivir has various effects on the central nervous system (CNS) that may be related to clinical findings including hypothermia, abnormal behaviours including with fatal outcome, and sudden death. Among receptors and enzymes related to CNS action, it is known that oseltamivir inhibits nicotinic acetylcholine receptors, which are closely related to hypothermia, as well as human monoamine oxidase-A (MAO-A), which is closely related to abnormal or excitatory behaviours. Receptors such as GABAA , GABAB and NMDA and their related receptors/channels including Na+ and Ca2+ channels are thought to be other candidates for investigation related to respiratory suppression followed by sudden death and psychotic reactions (both acute and chronic), respectively.

Abnormalities of serotonergic neurotransmission in animal models of SUDEP.

Sudden unexpected death in epilepsy (SUDEP) is a devastating event, and both DBA/1 and DBA/2 mice have been shown to be relevant animal models for studying SUDEP. DBA mice exhibit seizure-induced respiratory arrest (S-IRA), leading to cardiac arrest and subsequent sudden death after generalized audiogenic seizures (AGSs). This sequence of terminal events is also observed in the majority of witnessed human SUDEP cases. Several pathophysiological mechanisms, including respiratory/cardiac dysfunction, have been proposed to contribute to human SUDEP. Several (but not all) selective serotonin (5-HT) reuptake inhibitors (SSRIs), including fluoxetine, can reversibly block S-IRA, and abnormal expression of 5-HT receptors is found in the brainstem of DBA mice. DBA mice, which do not initially show S-IRA, exhibit S-IRA after treatment with a nonselective 5-HT antagonist. These studies suggest that abnormalities of 5-HT neurotransmission are involved in the pathogenesis of S-IRA in DBA mice. Serotonergic (5-HT) transmission plays an important role in normal respiration, and DBA mice exhibiting S-IRA can be resuscitated using a rodent ventilator. It is important and interesting to know if fluoxetine blocks S-IRA in DBA mice by enhancing respiratory ventilation. To test this, the effects of breathing stimulants, doxapram, and 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (PK-THPP) were compared with the effects of fluoxetine on S-IRA in DBA/1 mice. Although fluoxetine reduces the incidence of S-IRA in DBA/1 mice, as reported previously, the same dose of fluoxetine fails to enhance baseline respiratory ventilation in the absence of AGSs. Doxapram and PK-THPP augment the baseline ventilation in DBA/1 mice. However, these breathing stimulants are ineffective in preventing S-IRA in DBA/1 mice. These data suggest that fluoxetine blocks S-IRA in DBA/1 mice by cellular/molecular mechanisms other than enhancement of basal ventilation. Future research directions are also discussed. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

[Deaths from propofol abuse : Survey of institutes of forensic medicine in Germany, Austria and Switzerland]. / Todesfälle durch Propofolmissbrauch : Befragung in rechtsmedizinischen Instituten in Deutschland, Österreich und der Schweiz.

Previous references suggesting a high mortality of propofol addiction in medical personnel were mostly based on surveys of the heads of medical departments or case reports; therefore, a questionnaire was sent to 48 forensic medicine departments in Germany, Austria and Switzerland concerning the number of autopsies carried out between 2002-2112 on medical personnel with the suspicion of abuse of propofol or other analgesics. The response rate was 67%. In 16 out of the 32 responding departments 39 deaths (27 males) were observed with previous connections to anesthesiology, intensive care or emergency departments of which 22 were physicians, 13 nurses, 2 other personnel and 2 were unknown. Propofol was the major cause of death in 33 cases (85%), in 8 cases including 7 with propofol, an unintentional accident was recorded and 29 were determined to be suicide. In 14 cases chronic abuse was denied but actually excluded by toxicological analysis in only 2 cases. In 11 cases involving suicide the question of abuse was not investigated. This survey confirmed previous data about the central role of propofol for the fatal outcome of addiction and suicide of anesthetists and other medical personnel. A dual prevention strategy with low-threshold offers for persons at risk and strategies for early detection is urgently needed including a stricter control of dispensing, improvement in forensic medical documentation and the use of toxicological investigations in every case of suspected abuse.

Imidacloprid Poisoning: An Emerging Cause of Potentially Fatal Poisoning.

There are a variety of pesticides that are used to control the pests in agricultural lands and other places. Newer pesticides, developed as an alternative to highly toxic organophosphates such as imidacloprid including other neonicotinoid compounds, are being increasingly used considering their less harmful effects in case of human exposures. Though it is considered relatively safer to human beings, it can lead to potentially life-threatening complications and acute poisoning with these compounds may be fatal in large ingestion. We report a case of poisoning with imidacloprid compound presenting with a variety of systemic features including respiratory failure and patient's improvement with conservative management.

Paediatric apnoeas are not related to a specific respiratory virus, and parental reports predict hospitalisation.

AIM: The aim of this study was to determine the frequency of apnoeas in previously healthy young infants with acute respiratory tract infection (ARI) and correlate their occurrence with isolated micro-organisms, clinical findings, disease severity and outcome. METHODS: We performed reverse transcriptase real-time polymerase chain reaction (RT-PCR) on the nasal wash specimens of a prospective cohort study of 582 children with ARI. Clinical data on a subgroup of 241 infants under three months of age, with and without apnoeas, were compared. RESULTS: Our study found that 19 (7.9%) of the 241 infants under three months old had a history of apnoeas: eight had a respiratory syncytial virus (RSV), five had a different virus than RSV and seven RT-PCR results were negative. Infants with apnoeas were more likely to have cyanosis, had longer hospital stays and required extra oxygen for a longer period. Most patients with parental reported apnoeas also experienced apnoeas during hospitalisation. CONCLUSION: This study observed apnoeas irrespective of the isolated micro-organism, and we hypothesise that they were related to the pathophysiology of the respiratory infection and not to the micro-organism itself. Parental reported apnoeas were a major warning sign and predicted that apnoeas would occur in hospital.

Comparison of the combination of dexmedetomidine and ketamine to propofol or propofol/sevoflurane for drug-induced sleep endoscopy in children.

AIM: Examination of dynamic airway collapse in patients with obstructive sleep apnea (OSA) during drug-induced sleep endoscopy (DISE) can help identify the anatomic causes of airway obstruction. We hypothesized that a combination of dexmedetomidine and ketamine (Group DK) would result in fewer oxygen desaturations and a higher successful completion rate during DISE in children with OSA when compared to propofol (Group P) or sevoflurane/propofol (Group SP). METHODS: In this retrospective study, we reviewed the records of 59 children who presented for DISE between October 2013 and March 2015. Data analyzed included demographics, OSA severity, and hemodynamics (heart rate and blood pressure). The primary outcomes were airway desaturation during DISE to <85% and successful completion of DISE; these were compared between the three groups: DK, P, and SP. RESULTS: Preoperative polysomnography was available for 49 patients. There were significantly more patients with severe OSA in Group P as compared to the other two groups. The mean (±sd) bolus dose for ketamine, dexmedetomidine, and propofol were 2.0 ± 0.6 mg·kg(-1) , 1.9 ± 0.9 mcg·kg(-1) , and 1.8 ± 1.1 mg·kg(-1) , respectively. The mean (±sd) infusion rate for dexmedetomidine was 1.6 ± 0.7 mcg·kg(-1) ·h(-1) and for propofol was 248 ± 68 mcg·kg(-1) ·min(-1) in Group P and 192 ± 48 mcg·kg(-1) ·min(-1) in Group SP. Patients in Group DK had significantly fewer desaturations to <85% during DISE compared to Group P. Patients in Group DK had significantly more successful completion of DISE (100% Group DK, 92% Group P, and 79% Group SP) as compared to Group SP. CONCLUSIONS: These results suggest that the described dose regimen of propofol used alone or in combination with sevoflurane appears to be associated with more oxygen desaturations and a lower rate of successful completion than a combination of dexmedetomidine and ketamine during DISE in children with OSA.

Fluoxetine prevents respiratory arrest without enhancing ventilation in DBA/1 mice.

Sudden unexpected death in epilepsy (SUDEP) is a fatal epileptic event. DBA/1 mice are a relevant animal model for the study of SUDEP, as these mice exhibit seizure-induced respiratory arrest (S-IRA) leading to death, which has been observed in patients with witnessed SUDEP. Fluoxetine, a selective serotonin (5-hydroxytryptamine or 5-HT) reuptake inhibitor (SSRI), reduces S-IRA in DBA/1 mice. Given that DBA/1 mice with S-IRA can be resuscitated using a ventilator, we hypothesized that breathing stimulants can prevent S-IRA and that fluoxetine prevents S-IRA by enhancing ventilation in these mice. Spontaneous respiratory function in anesthetized or awake DBA/1 mice was examined using noninvasive plethysmography before and after administering fluoxetine or breathing stimulants, doxapram, and 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (PK-THPP). The effects of these drugs on S-IRA in DBA/1 mice were tested. As reported previously, systemic administration of fluoxetine reduced S-IRA in awake DBA/1 mice, but fluoxetine in anesthetized and awake DBA/1 mice did not increase basal ventilation or the ventilatory response to 7% CO2. Both doxapram and PK-THPP increased ventilation in room air and in air+7% CO2 in anesthetized DBA/1 mice. However, neither of the breathing stimulants reduced the incidence of S-IRA. Our studies confirm that fluoxetine reduces S-IRA in DBA/1 mice without enhancing basal ventilation in the absence of seizures. Although breathing stimulants increased ventilation in the absence of seizures, they were ineffective in reducing S-IRA, indicating that drug-induced increases in ventilation are insufficient to compensate for S-IRA in DBA/1 mice.

Clozapine-associated pneumonia and respiratory arrest secondary to severe constipation.

Clozapine is often the drug of choice within patients suffering from treatment-resistant paranoid schizophrenia. It has a complex side effects profile which includes potentially fatal agranulocytosis. Clozapine has also become increasingly associated with a range of other side effects including constipation and pneumonia. We report on a case of clozapine-induced severe constipation leading to a silent presentation of pneumonia with a subsequent respiratory arrest. To our knowledge, this is the first case report of pneumonia secondary to severe constipation occurring in the absence of respiratory aspiration of feculent vomitus. We suggest a new pathological mechanism by way of severe constipation leading to diaphragmatic dysfunction and subsequent clozapine-induced pneumonia. In addition, implications for clinical practice are outlined.