ORCID Profile
0000-0002-4398-2150
Current Organisations
Children's Hospital at Westmead
,
University of Sydney
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Publisher: Wiley
Date: 27-04-2018
DOI: 10.1111/PAN.13390
Abstract: There has been considerable interest in the possible adverse neurocognitive effects of exposure to general anesthesia and surgery in early childhood. The aim of this data linkage study was to investigate developmental and school performance outcomes of children undergoing procedures requiring general anesthesia in early childhood. We included children born in New South Wales, Australia of 37+ weeks' gestation without major congenital anomalies or neurodevelopmental disability with either a school entry developmental assessment in 2009, 2012, or Grade-3 school test results in 2008-2014. We compared children exposed to general anesthesia aged <48 months to those without any hospitalization. Children with only 1 hospitalization with general anesthesia and no other hospitalization were assessed separately. Outcomes included being classified developmentally high risk at school entry and scoring below national minimum standard in school numeracy and reading tests. Of 211 978 children included, 82 156 had developmental assessment and 153 025 had school test results, with 12 848 (15.7%) and 25 032 (16.4%) exposed to general anesthesia, respectively. Children exposed to general anesthesia had 17%, 34%, and 23% increased odds of being developmentally high risk (adjusted odds ratio [aOR]: 1.17 95% CI: 1.07-1.29) or scoring below the national minimum standard in numeracy (aOR: 1.34 95% CI: 1.21-1.48) and reading (aOR: 1.23 95% CI: 1.12-1.36), respectively. Although the risk for being developmentally high risk and poor reading attenuated for children with only 1 hospitalization and exposure to general anesthesia, the association with poor numeracy results remained. Children exposed to general anesthesia before 4 years have poorer development at school entry and school performance. While the association among children with 1 hospitalization with 1 general anesthesia and no other hospitalization was attenuated, poor numeracy outcome remained. Further investigation of the specific effects of general anesthesia and the impact of the underlying health conditions that prompt the need for surgery or diagnostic procedures is required, particularly among children exposed to long duration of general anesthesia or with repeated hospitalizations.
Publisher: Springer Science and Business Media LLC
Date: 15-08-2014
Publisher: BMJ
Date: 04-01-2013
DOI: 10.1136/BJSPORTS-2012-091752
Abstract: There remains considerable debate regarding the limiting factor(s) for maximal oxygen uptake (VO2max). Previous studies have shown that the central circulation may be the primary limiting factor for VO2max and that cardiac work increases beyond VO2max. We sought to evaluate whether the work of the heart limits VO2max during upright incremental cycle exercise to exhaustion. Eight trained men completed two incremental exercise trials, each terminating with exercise at two different rates of work eliciting VO2max (MAX and SUPRAMAX). During each exercise trial we continuously recorded cardiac output using pulse-contour analysis calibrated with a lithium dilution method. Intra-arterial pressure was recorded from the radial artery while pulmonary gas exchange was measured continuously for an assessment of oxygen uptake. The workload during SUPRAMAX (mean±SD: 346.5±43.2 W) was 10% greater than that achieved during MAX (315±39.3 W). There was no significant difference between MAX and SUPRAMAX for Q (28.7 vs 29.4 L/min) or VO2 (4.3 vs 4.3 L/min). Mean arterial pressure was significantly higher during SUPRAMAX, corresponding to a higher cardiac power output (8.1 vs 8.5 W p<0.06). Despite similar VO2 and Q, the greater cardiac work during SUPRAMAX supports the view that the heart is working submaximally at exhaustion during an incremental exercise test (MAX).
Publisher: Wiley
Date: 26-02-2019
DOI: 10.1111/PAN.13590
Publisher: Wiley
Date: 23-03-2022
DOI: 10.1111/PAN.14436
Publisher: Wiley
Date: 26-02-2019
DOI: 10.1111/PAN.13589
Abstract: This Statistical Analysis Plan details the statistical procedures to be applied for the analysis of data for the multicenter electroencephalography study. It consists of a basic description of the study in broad terms and separate sections that detail the methods of different aspects of the statistical analysis, summarized under the following headings (a) Background (b) Definitions of protocol violations (c) Definitions of objectives and other terms (d) Variables for analyses (e) Handling of missing data and study bias (f) Statistical analysis of the primary and secondary study outcomes (g) Reporting of study results and (h) References. It serves as a template for researchers interested in writing a Statistical Analysis Plan.
Publisher: Wiley
Date: 06-06-2015
DOI: 10.1111/PAN.12698
Publisher: Wiley
Date: 30-12-2019
DOI: 10.1111/PAN.13544
Abstract: Concern over potential neurotoxicity of anesthetics has led to growing interest in prospective clinical trials using potentially less toxic anesthetic regimens, especially for prolonged anesthesia in infants. Preclinical studies suggest that dexmedetomidine may have a reduced neurotoxic profile compared to other conventional anesthetic regimens however, coadministration with either anesthetic drugs (eg, remifentanil) and/or regional blockade is required to achieve adequate anesthesia for surgery. The feasibility of this pharmacological approach is unknown. The aim of this study was to determine the feasibility of a remifentanil/dexmedetomidine/neuraxial block technique in infants scheduled for surgery lasting longer than 2 hours. Sixty infants (age 1-12 months) were enrolled at seven centers over 18 months. A caudal local anesthetic block was placed after induction of anesthesia with sevoflurane. Next, an infusion of dexmedetomidine and remifentanil commenced, and the sevoflurane was discontinued. Three different protocols with escalating doses of dexmedetomidine and remifentanil were used. One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another. The caudal block was unsuccessful in two infants. Of the 56 infants who completed the protocol, 45 (80%) had at least one episode of hypertension (mean arterial pressure >80 mm Hg) and/or movement that required adjusting the anesthesia regimen. In the majority of these cases, the remifentanil and/or dexmedetomidine doses were increased although six infants required rescue 0.3% sevoflurane and one required a propofol bolus. Ten infants had at least one episode of mild hypotension (mean arterial pressure 40-50 mm Hg) and four had at least one episode of moderate hypotension (mean arterial pressure <40 mm Hg). A dexmedetomidine/remifentanil neuraxial anesthetic regimen was effective in 87.5% of infants. These findings can be used as a foundation for designing larger trials that assess alternative anesthetic regimens for anesthetic neurotoxicity in infants.
Publisher: Wiley
Date: 24-09-2016
DOI: 10.1111/PAN.13004
Abstract: Vascular complications following pediatric liver transplantation occur in 8-10% of cases, and no continuous, non-invasive monitoring for this problem exists. Near infrared spectroscopy (NIRS) allows non-invasive, continuous, transcutaneous assessment of hemoglobin oxygenation (StO We hypothesized that transcutaneous NIRS would be able to detect severe hepatic ischemia, and tested this in an animal model using 15-20 kg and 5-7 kg juvenile pigs. Direct liver surface and transcutaneous hepatic tissue hemoglobin oxygen saturation (StO In the 15-20 kg animals during complete occlusion, CutHepStO Transcutaneous hepatic StO
Publisher: Wiley
Date: 12-2018
DOI: 10.1111/PAN.13520
Publisher: Wiley
Date: 04-03-2011
Publisher: Wiley
Date: 20-12-2020
DOI: 10.1111/PAN.13766
Publisher: Springer Science and Business Media LLC
Date: 29-10-2020
DOI: 10.1007/S00228-020-03028-2
Abstract: The purpose of this international study was to investigate prescribing practices of dexmedetomidine by paediatric anaesthesiologists. We performed an online survey on the prescription rate of dexmedetomidine, route of administration and dosage, adverse drug reactions, education on the drug and overall experience. Members of specialist paediatric anaesthesia societies of Europe (ESPA), New Zealand and Australia (SPANZA), Great Britain and Ireland (APAGBI) and the USA (SPA) were consulted. Responses were collected in July and August 2019. Data from 791 responders (17% of 5171 invitees) were included in the analyses. Dexmedetomidine was prescribed by 70% of the respondents (ESPA 53% SPANZA 69% APAGBI 34% and SPA 96%), mostly for procedural sedation (68%), premedication (46%) and/or ICU sedation (46%). Seventy-three percent had access to local or national protocols, although lack of education was the main reason cited by 26% of the respondents not to prescribe dexmedetomidine. The main difference in dexmedetomidine use concerned the age of patients (SPA primarily 1 year, others primarily 1 year). The dosage varied widely ranging from 0.2–5 μg kg −1 for nasal premedication, 0.2–8 μg kg −1 for nasal procedural sedation and 0–4 μg kg −1 intravenously as adjuvant for anaesthesia. Only ESPA members (61%) had noted an adverse drug reaction, namely bradycardia. The majority of anaesthesiologists use dexmedetomidine in paediatrics for premedication, procedural sedation, ICU sedation and anaesthesia, despite the off-label use and sparse evidence. The large intercontinental differences in prescribing dexmedetomidine call for consensus and worldwide education on the optimal use in paediatric practice.
Publisher: Medpharm Publications
Date: 02-2005
Publisher: Medpharm Publications
Date: 02-2003
Publisher: Informa UK Limited
Date: 25-06-2015
DOI: 10.3109/14756366.2014.920839
Abstract: Falcipain-2 (FP-2) is a key cysteine protease from the malaria parasite Plasmodium falciparum. Many previous studies have identified FP-2 inhibitors however, none has yet met the criteria for an antimalarial drug candidate. In this work, we assayed an in-house library of non-peptidic organic compounds, including (E)-chalcones, (E)-N'-benzylidene-benzohydrazides and alkyl-esters of gallic acid, and assessed the activity toward FP-2 and their mechanisms of inhibition. The (E)-chalcones 48, 54 and 66 showed the lowest IC50 values (8.5 ± 0.8 µM, 9.5 ± 0.2 µM and 4.9 ± 1.3 µM, respectively). The best inhibitor (compound 66) demonstrated non-competitive inhibition, and using mass spectrometry and fluorescence spectroscopy assays, we suggest a potential allosteric site for the interaction of this compound, located between the catalytic site and the hemoglobin binding arm in FP-2. We combined structural biology tools and mass spectrometry to characterize the inhibition mechanisms of novel compounds targeting FP-2.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2003
DOI: 10.1097/01.ACO.0000084473.59960.87
Abstract: This review focuses on recent knowledge in areas of anaesthesia expertise which are indispensable to intensive care unit management, including airway management, vascular access, regional analgesia and the treatment of status asthmaticus and status epilepticus. Etomidate as the sole agent for intubation in the intensive care unit has a 90% success rate, while in a prehospital setting, the addition of succinylcholine to etomidate results in a 99% success rate. In determining successful intubation, capnography and laryngoscopic/fibreoptic visualization are superior to auscultation, while auscultation is as effective as the self-inflating bulb or transillumination with the lightwand. The dorsalis pedis artery is an effective alternative to radial artery cannulation, while arterial cannulation itself can result in major adverse effects if complications arise. Ultrasound guidance in the placement of central catheters results in an improved insertion success rate. Internal jugular and subclavian lines have similar risk of haemothorax or pneumothorax, while subclavian lines are associated with the lowest incidence of infection. Midazolam, thiopentone and propofol have all been found to be efficacious in terminating refractory status epilepticus, with thiopentone resulting in a lower incidence of breakthrough seizures or treatment failure but an increased incidence of hypotension. Inhalational anaesthesia using isoflurane or desflurane has also been found to be successful in refractory status epilepticus. In the management of status asthmaticus, limiting minute volume while tolerating hypercapnia and acidosis as well as the use of inhalational anesthesia have proven effective strategies in a number of refractory cases. The anaesthesiologist's unique knowledge and skills are ideally suited to the practical management of patients in a critical care setting as well as in the treatment of the critical phases of many illnesses.
Publisher: Springer Science and Business Media LLC
Date: 03-10-2014
Publisher: Wiley
Date: 02-01-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2017
Publisher: Wiley
Date: 15-02-2022
DOI: 10.1111/PAN.14372
Publisher: IOP Publishing
Date: 18-09-2012
DOI: 10.1088/0967-3334/33/10/1691
Abstract: The aim of this study was to evaluate the use of pulse contour analysis calibrated with lithium dilution in a single device (LiDCO) for measurement of cardiac output (Q) during exercise in healthy volunteers. We sought to (a) compare pulse contour analysis (PulseCO) and lithium indicator dilution (LiDCO) for the measurement of Q during exercise, and (b) assess the requirement for recalibration of PulseCO with LiDCO during exercise. Ten trained males performed multi-stage cycling exercise at intensities below and above ventilatory threshold before constant load maximal exercise to exhaustion. Uncalibrated PulseCO Q (Qraw) was compared to that calibrated with lithium dilution at baseline Qbaseline, during submaximal exercise below (Qlow) and above (Qhigh) ventilatory threshold, and at each exercise stage in idually (Qexercise). There was a significant difference between Qbaseline and all other calibration methods during exercise, but not at rest. No significant differences were observed between other methods. Closest agreement with Qexercise was observed for Qhigh (bias ± limits of agreement: 4.8 ± 30.0%). The difference between Qexercise and both Qlow and Qraw was characterized by low bias (4-7%) and wide limits of agreement (> ± 40%). Calibration of pulse contour analysis with lithium dilution prior to exercise leads to a systematic overestimation of exercising cardiac output. A single calibration performed during exercise above the ventilatory threshold provided acceptable limits of agreement with an approach incorporating multiple calibrations throughout exercise. Pulse contour analysis may be used for Q measurement during exercise providing the system is calibrated during exercise.
Publisher: Wiley
Date: 28-08-2016
DOI: 10.1111/PAN.13000
Abstract: Peripheral vasodilation is a well-recognized side effect of general anesthesia, and induces changes in the litude of the pulse plethysmograph (PPG) waveform. This can be continuously quantitaed using the Perfusion Index (PI), a ratio of the pulsatile to nonpulsatile signal litude in the PPG waveform. We hypothesized that the perfusion index would rise with the induction of anesthesia in children, and fall with emergence, and performed a prospective, observational study to test this. Our primary aim was to test whether the different clinical stages of anesthesia were associated with changes in the perfusion index, and the secondary aim was to test the correlation between the normalized perfusion index and the MAC value. Twenty-one patients between the ages of 1 and 18 undergoing minor procedures with no anticipated painful stimuli were recruited. Patients with significant illnesses were excluded. Data collection commenced with a preinduction baseline, and data were collected continuously, with event marking, until completion of the anesthesia and removal of the pulse oximeter. Data collected included perfusion index, heart rate, and anesthetic gas concentration values. A normalized perfusion index was calculated by subtracting the initial baseline perfusion index value from all perfusion index values, allowing changes, from a standardized initial baseline value of zero, to be analyzed. During induction, the mean normalized perfusion index rose from 0.0 to 4.2, and then declined to 0.470 when the patients returned to consciousness. P < 0.001 using repeated measures anova test. The normalized perfusion index was correlated with MAC values (r The perfusion index changed significantly during different stages of anesthesia. There is a significant correlation between the perfusion index, measured by pulse oximetry, and the MAC value, in pediatric patients undergoing minor procedures.
Publisher: IOP Publishing
Date: 20-02-2014
DOI: 10.1088/0967-3334/35/3/471
Abstract: Children suffering supracondylar fractures of the humerus are at risk of vascular compromise, which is currently assessed clinically, although other modalities such as angiography, pulse oximetry, Doppler ultrasound and magnetic resonance angiography have been used. We sought to ascertain whether tissue haemoglobin oxygenation (StO2) measurement could distinguish between patients with and without clinical vascular compromise following supracondylar fractures of the humerus. We prospectively observed StO2 using near-infrared spectroscopy in 29 paediatric patients with supracondylar fractures requiring operative manipulation. The injured and uninjured volar forearm compartments were monitored immediately before and after fracture reduction. The relationship between StO2 in the injured and uninjured limb, and the presence of pre-operative vascular compromise was assessed. Seven out of 29 children presented with vascular compromise. Patients with clinical vascular compromise had significantly lower pre-reduction StO2 (63.5% ± 15%, mean ± standard deviation), compared to those without compromise (80.9% ± 10%). StO2 normalized following surgery in all children with vascular compromise. These improvements in muscle StO2 were associated, in all patients, with the clinical return of pulses and resolution of neurological symptoms if present. StO2 monitoring can identify patients with clinical vascular compromise, can identify the return of adequate perfusion following operative correction of supracondylar fractures, and may be a useful adjunct to clinical assessment.
Publisher: Wiley
Date: 21-02-2017
DOI: 10.1111/PAN.13087
Publisher: Wiley
Date: 06-10-2008
DOI: 10.1111/J.1460-9592.2008.02720.X
Abstract: Maintenance of cardiovascular stability is crucial to safe anesthetic practice, but measurement of cardiac output has been technically challenging, particularly in pediatric patients. Cardiovascular monitoring has therefore generally relied upon pressure-based measurements, as opposed to flow-based measurements. The measurement of cardiac output under anesthesia and in critical care has recently become easier as a result of new techniques of measurement. This article reviews the basic concepts of and rationale for cardiac output monitoring, and then describes the techniques available for monitoring in clinical practice.
Publisher: Wiley
Date: 12-2015
DOI: 10.1111/PAN.12800
Abstract: Near-infrared spectroscopy (NIRS) provides an assessment of cerebral oxygenation and tissue hemoglobin concentration. The aim of this study was to investigate whether the cerebral oxygenation and hemoglobin concentration measured with NIRS could predict outcomes after pediatric cardiac surgery. We conducted a retrospective observational study in 399 patients who underwent pediatric cardiac surgery. Associations were determined between postoperative outcome and preoperative and postoperative cerebral tissue oxygenation index (TOI), postoperative normalized tissue hemoglobin index (nTHI), concentration changes in oxygenated hemoglobin (Δ[HbO2 ]) and deoxygenated hemoglobin (Δ[HHb]). Thirty-nine children had major postoperative morbidity and 12 died. Using Spearman's correlation analysis, postoperative lower TOI and higher Δ[HHb] were associated with longer stays in the Intensive Care Unit (ICU) (r = -0.48, P < 0.001, r = 0.31, P < 0.001, respectively) and longer duration of intubation (r = -0.48, P < 0.001, r = 0.31, P < 0.001, respectively) and higher probability of death determined by the Risk Adjusted Classification for Congenital Heart Surgery (RACHS-1) (r = -0.39, P < 0.001, r = 0.23, P < 0.001, respectively). In multivariate regression analysis, postoperative TOI was independently associated with major morbidity and mortality and Δ[HHb] was independently associated with major morbidity. In receiver operating characteristic analysis, postoperative TOI and Δ[HHb] predicted major morbidity (Area under the curve [AUC] = 0.72, 0.68, respectively) and mortality (AUC = 0.81, 0.69, respectively). Lower TOI or higher [HHb] at the end of surgery and higher RACHS-1 category predicted worse outcomes.
Publisher: Wiley
Date: 12-09-2012
DOI: 10.1111/PAN.12007
Abstract: This article reviews potential pediatric applications of 3 new technologies. (1) Pulse oximetry-based hemoglobin determination: Hemoglobin determination using spectrophotometric methods recently has been introduced in adults with varied success. This non-invasive and continuous technology may avoid venipuncture and unnecessary transfusion in children undergoing surgery with major blood loss, premature infants undergoing unexpected and complicated emergency surgery, and children with chronic illness. (2) Continuous cardiac output monitoring: In adults, advanced hemodynamic monitoring such as continuous cardiac output monitoring has been associated with better surgical outcomes. Although it remains unknown whether similar results are applicable to children, current technology enables the monitoring of cardiac output non-invasively and continuously in pediatric patients. It may be important to integrate the data about cardiac output with other information to facilitate therapeutic interventions. (3) Anesthesia information management systems: Although perioperative electronic anesthesia information management systems are gaining popularity in operating rooms, their potential functions may not be fully appreciated. With advances in information technology, anesthesia information management systems may facilitate bedside clinical decisions, administrative needs, and research in the perioperative setting.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2018
DOI: 10.1097/ALN.0000000000001920
Abstract: General anesthesia during infancy is associated with neurocognitive abnormalities. Potential mechanisms include anesthetic neurotoxicity, surgical disease, and cerebral hypoxia–ischemia. This study aimed to determine the incidence of low cerebral oxygenation and associated factors during general anesthesia in infants. This multicenter study enrolled 453 infants aged less than 6 months having general anesthesia for 30 min or more. Regional cerebral oxygenation was measured by near-infrared spectroscopy. We defined events (more than 3 min) for low cerebral oxygenation as mild (60 to 69% or 11 to 20% below baseline), moderate (50 to 59% or 21 to 30% below baseline), or severe (less than 50% or more than 30% below baseline) for low mean arterial pressure as mild (36 to 45 mmHg), moderate (26 to 35 mmHg), or severe (less than 25 mmHg) and low pulse oximetry saturation as mild (80 to 89%), moderate (70 to 79%), or severe (less than 70%). The incidences of mild, moderate, and severe low cerebral oxygenation were 43%, 11%, and 2%, respectively mild, moderate, and severe low mean arterial pressure were 62%, 36%, and 13%, respectively and mild, moderate, and severe low arterial saturation were 15%, 4%, and 2%, respectively. Severe low oxygen saturation measured by pulse oximetry was associated with mild and moderate cerebral desaturation American Society of Anesthesiology Physical Status III or IV versus I was associated with moderate cerebral desaturation. Severe low cerebral saturation events were too infrequent to analyze. Mild and moderate low cerebral saturation occurred frequently, whereas severe low cerebral saturation was uncommon. Low mean arterial pressure was common and not well associated with low cerebral saturation. Unrecognized severe desaturation lasting 3 min or longer in infants seems unlikely to explain the subsequent development of neurocognitive abnormalities.
No related grants have been discovered for Justin Skowno.