Anaesthesia with dexmedetomidine and remifentanil in a child with mitochondrial myopathy

Patients with mitochondrial disorders have complex physiological issues which create a challenging scenario with regard to the safe provision of anaesthetic care. Within the spectrum of mitochondrial disorders, patients can be susceptible to multiple adverse effects and drug reactions from medications used during general anaesthesia. Although recent evidence suggests that inhalational anaesthetic agents may be used in patients with mitochondrial disorders, there is still a preference among some anaesthesia providers to use total intravenous anaesthesia (TIVA). In most scenarios, when TIVA is chosen, propofol is a major component. However, as a result of using propofol, patients with mitochondrial disorders may be susceptible to an acute metabolic crisis. It has been postulated that propofol, especially when given in large dosages, or when infused for prolonged periods of time, can adversely affect the function of the abnormal mitochondria that are present in patients with mitochondrial disorders. We present our experience with the use of dexmedetomidine as the primary component of a general anaesthetic regimen in a 10-year-old girl with a mitochondrial disorder and dystonia, who required anaesthetic care during a urological procedure. Previous reports on the use of dexmedetomidine as part of TIVA in patients susceptible to malignant hyperthermia are reviewed, and its benefits in patients with mitochondrial disorders, discussed. Additional concerns regarding the perioperative care of patients with mitochondrial disorders are deliberated.Keywords: dexmedetomidine, malignant hyperthermia, mitochondrial myopath

Perioperative care of a child with tetanus

Tetanus is caused by tetanospasmin, a toxin that is produced by the anaerobic bacterium, Clostridium tetani. Despite widespread vaccination, which limits its incidence in many parts of the world, tetanus may still occur owing to lack of immunisation related to religious tenets, cultural beliefs or inaccessibility to medical care. Of major concern during the perioperative care of such patients is control of the muscle spasms and the propensity for autonomic dysfunction, resulting in blood pressure instability. Ongoing muscle spasms may impair upper airway control or respiratory muscle function, thereby resulting in respiratory failure. Autonomic dysfunction may result in profound hypertension followed by hypotension, bradycardia and asystole. The pathophysiology of tetanus, its clinical manifestations, and current treatment options are discussed. The preoperative implications of tetanus and the care of these patients are reviewed.South Afr J Anaesth Analg, 2011;17(6):380-38

Withdrawal symptoms in children after long-term administration of sedatives and/or analgesics: A literature review. "Assessment remains troublesome"

Background: Prolonged administration of benzodiazepines and/or opioids to children in a pediatric intensive care unit (PICU) may induce physiological dependence and withdrawal symptoms. Objective: We reviewed the literature for relevant contributions on the nature of these withdrawal symptoms and on availability of valid scoring systems to assess the extent of symptoms. Methods: The databases PubMed, CINAHL, and Psychinfo (1980-June 2006) were searched using relevant key terms. Results: Symptoms of benzodiazepine and opioid withdrawal can be classified in two groups: central nervous system effects and autonomic dysfunction. However, symptoms of the two types show a large overlap for benzodiazepine and opioid withdrawal. Symptoms of gastrointestinal dysfunction in the PICU population have been described for opioid withdrawal only. Six assessment tools for withdrawal symptoms are used in children. Four of these have been validated for neonates only. Two instruments are available to specifically determine withdrawal symptoms in the PICU: the Sedation Withdrawal Score (SWS) and the Opioid Benzodiazepine Withdrawal Scale (OBWS). The OBWS is the only available assessment tool with prospective validation; however, the sensitivity is low. Conclusions: Withdrawal symptoms for benzodiazepines and opioids largely overlap. A sufficiently sensitive instrument for assessing withdrawal symptoms in PICU patients needs to be developed

Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients

<p>Abstract</p> <p>Background</p> <p>Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children.</p> <p>Methods</p> <p>Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints.</p> <p>Results</p> <p>Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0–1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined.</p> <p>Conclusion</p> <p>Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8–1.2 mcg/kg/min) than as labeled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.</p

The correlation and level of agreement between end-tidal and blood gas pCO2 in children with respiratory distress: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>To investigate the correlation and level of agreement between end-tidal carbon dioxide (EtCO₂) and blood gas pCO₂in non-intubated children with moderate to severe respiratory distress.</p> <p>Methods</p> <p>Retrospective study of patients admitted to an intermediate care unit (InCU) at a tertiary care center over a 20-month period with moderate to severe respiratory distress secondary to asthma, bronchiolitis, or pneumonia. Patients with venous pCO₂(vpCO₂) and EtCO₂measurements within 10 minutes of each other were eligible for inclusion. Patients with cardiac disease, chronic pulmonary disease, poor tissue perfusion, or metabolic abnormalities were excluded.</p> <p>Results</p> <p>Eighty EtCO₂-vpCO₂paired values were available from 62 patients. The mean ± <smcaps>SD</smcaps> for EtCO₂and vpCO₂was 35.7 ± 10.1 mmHg and 39.4 ± 10.9 mmHg respectively. EtCO₂and vpCO₂values were highly correlated (r = 0.90, p < 0.0001). The correlations for asthma, bronchiolitis and pneumonia were 0.74 (p < 0.0001), 0.83 (p = 0.0002) and 0.98 (p < 0.0001) respectively. The mean bias ± <smcaps>SD</smcaps> between EtCO₂and vpCO₂was -3.68 ± 4.70 mmHg. The 95% level of agreement ranged from -12.88 to +5.53 mmHg. EtCO₂was found to be more accurate when vpCO₂was 35 mmHg or lower.</p> <p>Conclusion</p> <p>EtCO₂is correlated highly with vpCO₂in non-intubated pediatric patients with moderate to severe respiratory distress across respiratory illnesses. Although the level of agreement between the two methods precludes the overall replacement of blood gas evaluation, EtCO₂monitoring remains a useful, continuous, non-invasive measure in the management of non-intubated children with moderate to severe respiratory distress.</p

An Integrated-Photonics Optical-Frequency Synthesizer

Integrated-photonics microchips now enable a range of advanced functionalities for high-coherence applications such as data transmission, highly optimized physical sensors, and harnessing quantum states, but with cost, efficiency, and portability much beyond tabletop experiments. Through high-volume semiconductor processing built around advanced materials there exists an opportunity for integrated devices to impact applications cutting across disciplines of basic science and technology. Here we show how to synthesize the absolute frequency of a lightwave signal, using integrated photonics to implement lasers, system interconnects, and nonlinear frequency comb generation. The laser frequency output of our synthesizer is programmed by a microwave clock across 4 THz near 1550 nm with 1 Hz resolution and traceability to the SI second. This is accomplished with a heterogeneously integrated III/V-Si tunable laser, which is guided by dual dissipative-Kerr-soliton frequency combs fabricated on silicon chips. Through out-of-loop measurements of the phase-coherent, microwave-to-optical link, we verify that the fractional-frequency instability of the integrated photonics synthesizer matches the $7.0*10^{-13}$ reference-clock instability for a 1 second acquisition, and constrain any synthesis error to $7.7*10^{-15}$ while stepping the synthesizer across the telecommunication C band. Any application of an optical frequency source would be enabled by the precision optical synthesis presented here. Building on the ubiquitous capability in the microwave domain, our results demonstrate a first path to synthesis with integrated photonics, leveraging low-cost, low-power, and compact features that will be critical for its widespread use.Comment: 10 pages, 6 figure

Construction of the Sophia Observation withdrawal Symptoms-scale (SOS) for critically ill children

Objective: To construct a reliable and clinically practical instrument for monitoring opioids and benzodiazepine withdrawal symptoms in pediatric ICU patients. Design: Instrument development. Setting: Intensive care unit in an academic children's hospital. Patients and participants: 79 patients up to age 16 years on intravenous midazolam and/or opioids for ≥5 days. An expert panel of 85 physicians and nurses rated clinical relevance of withdrawal symptoms. Intervention: During drug weaning repeated observations were performed with a checklist of 24 withdrawal symptoms described in the literature. Measurements and results: For 76 children, 932 observations were obtained within 24 h after decrease and/or discontinuation of midazolam or opioids. Most frequent symptoms were tachypnea, agitation, motor disturbance, diarrhea, fever, anxiety, sleep disturbance and hypertension (14.6-29.6%). Multidimensional scaling (MDS) was performed to detect the underlying empirical structure of co-occurrences of symptoms. An expert panel judged clinical relevance of each withdrawal symptom on a four-point scale ranging from 'definitively so' to 'definitively not'. Agitation, an

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors