ORCID Profile
0000-0001-9803-9701
Current Organisations
University of Queensland
,
Royal Brisbane and Women's Hospital
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Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.PUPT.2018.04.006
Abstract: Preservative-free tobramycin is commonly used as aerosolized therapy for ventilator associated pneumonia. The comparative delivery profile of the formulations of two different concentrations (100 mg/ml and 40 mg/ml) is unknown. This study aims to evaluate the aerosol characteristics of these tobramycin formulations in a simulated adult mechanical ventilation model. Simulated adult mechanical ventilation set up and optimal settings were used in the study. Inhaled mass study was performed using bacterial/viral filters at the tip of the tracheal tube and in the expiratory limb of circuit. Laser diffractometer was used for characterising particle size distribution. The physicochemical characteristics of the formulations were described and nebulization characteristics compared using two airways, an endotracheal tube (ET) and a tracheostomy tube (TT). For each type of tube, three internal tube diameters were studied, 7 mm, 8 mm and 9 mm. The lung dose was significantly higher for 100 mg/ml solution (mean 121.3 mg vs 41.3 mg). Viscosity was different (2.11cp vs 1.58cp) for 100 mg/ml vs 40 mg/ml respectively but surface tension was similar. For tobramycin 100 mg/ml vs 40 mg/ml, the volume median diameter (2.02 vs 1.9 μm) was comparable. The fine particle fraction (98.5 vs 85.4%) was higher and geometric standard deviation (1.36 vs 1.62 μm) was significantly lower for 100 mg/ml concentration. Nebulization duration was longer for 100 mg/ml solution (16.9 vs 10.1 min). The inhaled dose percent was similar (30%) but the exhaled dose was higher for 100 mg/ml solution (18.9 vs 10.4%). The differences in results were non-significant for type of tube or size except for a small but statistically significant reduction in inhaled mass with TT compared to ET (0.06%). Aerosolized tobramycin 100 mg/ml solution delivered higher lung dose compared to tobramycin 40 mg/ml solution. Tracheal tube type or size did not influence the aerosol characteristics and delivery parameters.
Publisher: Wiley
Date: 05-2020
DOI: 10.1111/IMJ.14721
Abstract: Neutropenic fever is a frequently encountered complication when caring for cancer patients and can lead to intensive care admission, with high mortality rates in those patients who require invasive mechanical ventilation (IMV). Although hospital survival in this population has improved, long-term outcomes of critically ill neutropenic cancer patients have not been well defined. To evaluate short- and long-term outcomes of neutropenic cancer patients admitted to intensive care, according to requirement for invasive ventilation. Additionally, we aimed to determine predictors of poor clinical outcomes in this group. A retrospective cohort study of neutropenic cancer patients admitted to our intensive care unit (ICU) from 2008 to 2016. We included 192 cancer patients of whom 100 (52.1%) required IMV. Overall ICU mortality was 29.7% and 12-month post-ICU mortality was 61.5%. Patients requiring IMV had significantly higher short- and long-term mortality (P < 0.001). Multivariate analysis determined three variables to be predictors of mortality at ICU discharge in the whole cohort: IMV (OR 13.52), renal replacement therapy (RRT, OR 2.37) and higher APACHE II scores (OR 1.1 for each unit increase). These variables were identical in the subgroup requiring invasive ventilation, with RRT (OR 2.76) and APACHE II scores (OR 1.1 for each unit increase) predicting short-term mortality. Neutropenic cancer patients admitted to ICU have lower short-term mortality than previously reported in cohort studies, however their mortality rises significantly following discharge from ICU. Those patients who require IMV are at significantly increased risk of both short- and long-term mortality.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.IJANTIMICAG.2018.11.011
Abstract: Knowledge of antibiotic concentrations achievable in the epithelial lining fluid (ELF) will help guide antibiotic dosing for treating patients with Gram-negative bacillary ventilator-associated pneumonia (VAP). To compare: (1) the ELF:serum penetration ratio of antibiotics in patients with pneumonia, including VAP, with that in healthy study participants and (2) the ELF and/or tracheal aspirate antibiotic concentrations following intravenous and nebuliser delivery. Web of Science, EMBASE and PubMed databases were searched and a systematic review undertaken. Fifty-two studies were identified. ELF penetration ratios for aminoglycosides and most β-lactam antibiotics administered intravenously were between 0.12 and 0.57, whereas intravenous colistin may be undetectable in the ELF. In contrast, estimated mean fluoroquinolone ELF penetration ratios of up to 1.31 were achieved. Importantly, ELF penetration ratios appear reduced in critically ill patients with pneumonia compared with in healthy volunteers receiving intravenous ceftazidime, levofloxacin and fosfomycin thus, dose adjustment is likely to be required in critically ill patients. In contrast to the systemic administration route, nebulisation of antibiotics achieves high ELF concentrations. Nebulised 400 mg twice-daily amikacin resulted in a median peak ELF steady-state concentration of 976.01 mg/L (interquartile range 410.3-2563.1 mg/L). Similarly, nebulised 1 million international units of colistin resulted in a peak ELF concentration of 6.73 mg/L (interquartile range 4.80-10.10 mg/L). Further pharmacokinetic studies investigating the mechanisms for ELF penetration in infected patients and healthy controls are needed to guide antibiotic dosing in VAP and to determine the potential benefits of nebulised therapy.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1093/BJA/AEL286
Abstract: The central venous catheter (CVC) is associated with numerous complications more so during the process of insertion. We report for the first time how an indwelling catheter was entrapped by a replacement catheter on the same side, after being speared by the introducer needle and guidewire. The diagnosis was made when there was difficulty in removing the old catheter. Subsequently, interventional radiology services were used to define the problem and help in removal of the entrapped catheter. The mechanism of entrapment and the actual procedure used for removal of the catheter is described. The dangers of insertion of a CVC on the same side as a pre-existing one are highlighted.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2017
DOI: 10.1097/ALN.0000000000001570
Abstract: Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients. A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded. Five of the 11 studies included had a small s le size (fewer than 50 patients), and only 6 were randomized. Diversity of case-mix, dosage, and devices are sources of bias. Only a few patients had severe hypoxemia. Aminoglycosides and colistin were the most common antibiotics, being safe regarding nephrotoxicity and neurotoxicity, but increased respiratory complications in 9% (95% CI, 0.01 to 0.18 I2 = 52%), particularly when administered to hypoxemic patients. For tracheobronchitis, a significant decrease in emergence of resistance was evidenced (risk ratio, 0.18 95% CI, 0.05 to 0.64 I2 = 0%). Similar findings were observed in pneumonia by susceptible pathogens, without improvement in mortality or ventilation duration. In pneumonia caused by resistant pathogens, higher clinical resolution (odds ratio, 1.96 95% CI, 1.30 to 2.96 I2 = 0%) was evidenced. These findings were not consistently evidenced in the assessment of efficacy against pneumonia caused by susceptible pathogens. Performance of randomized trials evaluating the impact of nebulized antibiotics with more homogeneous populations, standardized drug delivery, predetermined clinical efficacy, and safety outcomes is urgently required. Infections by resistant pathogens might potentially have higher benefit from nebulized antiinfective agents. Nebulization, without concomitant systemic administration of the drug, may reduce nephrotoxicity but may also be associated with higher risk of respiratory complications.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.CMI.2017.04.011
Abstract: With an established role in cystic fibrosis and bronchiectasis, nebulized antibiotics are increasingly being used to treat respiratory infections in critically ill invasively mechanically ventilated adult patients. Although there is limited evidence describing their efficacy and safety, in an era when there is a need for new strategies to enhance antibiotic effectiveness because of a shortage of new agents and increases in antibiotic resistance, the potential of nebulization of antibiotics to optimize therapy is considered of high interest, particularly in patients infected with multidrug-resistant pathogens. This Position Paper of the European Society of Clinical Microbiology and Infectious Diseases provides recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology regarding the use of nebulized antibiotics in invasively mechanically ventilated adults, based on a systematic review and meta-analysis of the existing literature (last search July 2016). Overall, the panel recommends avoiding the use of nebulized antibiotics in clinical practice, due to a weak level of evidence of their efficacy and the high potential for underestimated risks of adverse events (particularly, respiratory complications). Higher-quality evidence is urgently needed to inform clinical practice. Priorities of future research are detailed in the second part of the Position Paper as guidance for researchers in this field. In particular, the panel identified an urgent need for randomized clinical trials of nebulized antibiotic therapy as part of a substitution approach to treatment of pneumonia due to multidrug-resistant pathogens.
Publisher: S. Karger AG
Date: 2019
DOI: 10.1159/000502474
Abstract: Extra-corporeal membrane oxygenation (ECMO) therapy could affect effective drug concentrations via adsorption onto the oxygenator or associated circuit. We describe a case of a 25-year-old female who required a veno-arterial ECMO therapy for refractory cardiac arrest due to massive pulmonary embolism. She had mild renal dysfunction as a result of the cardiac arrest. A total of 2 g of intravenous cefazolin 8-hourly was administered. Pre- and post-oxygenator blood s les were collected at 0, 1, 4, and 8 h post antibiotic administration. S les were analyzed for total and unbound cefazolin concentrations. Protein binding was ∼60%. Clearance was reduced due to impaired renal function. The pharmacokinetics of cefazolin appear to not be affected by ECMO therapy and dosing adjustment may not be required.
Publisher: Springer Science and Business Media LLC
Date: 11-07-2018
Publisher: University of Queensland Library
Date: 2019
DOI: 10.14264/UQL.2019.61
Publisher: Mary Ann Liebert Inc
Date: 04-2017
Abstract: Mechanically ventilated patients commonly suffer from ventilator-associated pneumonia, hypoxemia, and other lower respiratory tract infection as a result of pathogen colonization and poor sputum clearance. Consequently, there is a high rate of morbidity and mortality in these patients. Dry powder mannitol increases sputum clearance, and therefore, we developed a system to administer it to mechanically ventilated patients without disconnection from the ventilator. The inspiratory line from a ventilator was split by using a three-way valve into two parallel lines where one contains a humidifier for normal breathing cycle and the other line contains a dry powder inhaler (Osmohaler™). The inspiratory air went through the dry powder line and aerosolized the mannitol powder only when its administration to a patient is required. We determined the delivered dose and particle size distributions of emitted aerosols in vitro from 9.5 mm endotracheal and 7.5 mm tracheostomy tubes, with inspiratory airflow of 60, 70, and 80 L/min. This novel setup was able to deliver 24.6% ± 3.33% of the 160 mg loaded dose mannitol powder (4 × 40 mg capsules) and 26.7% ± 2.19% of the 320 mg dose (4 × 80 mg capsules) when the endotracheal tube was used. With the shorter tracheostomy tube, the delivery dose increased to 35.6% ± 3.01% and 39.5% ± 2.04% of the 160 and 320 mg doses, respectively. The volume median diameters of the aerosols were in the respirable range with the largest value being 5.17 ± 0.87 μm. This delivery system has been shown to consistently deliver a high respirable dose of mannitol powder. Since this setup does not require disconnection of patients from the ventilator, it is safer for hypoxemic patients and easier to be adapted in a real clinical use.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2019
DOI: 10.1097/ALN.0000000000002752
Abstract: Nebulized antibiotics may be used to treat ventilator-associated pneumonia. In previous pharmacokinetic studies, lung interstitial space fluid concentrations have never been reported. The aim of the study was to compare intravenous and nebulized tobramycin concentrations in the lung interstitial space fluid, epithelial lining fluid, and plasma in mechanically ventilated sheep with healthy lungs. Ten anesthetized and mechanically ventilated healthy ewes underwent surgical insertion of microdialysis catheters in upper and lower lobes of both lungs and the jugular vein. Five ewes were given intravenous tobramycin 400 mg, and five were given nebulized tobramycin 400 mg. Microdialysis s les were collected every 20 min for 8 h. Bronchoalveolar lavage was performed at 1 and 6 h. The peak lung interstitial space fluid concentrations were lower with intravenous tobramycin 20.2 mg/l (interquartile range, 12 mg/l, 26.2 mg/l) versus the nebulized route 48.3 mg/l (interquartile range, 8.7 mg/l, 513 mg/l), P = 0.002. For nebulized tobramycin, the median epithelial lining fluid concentrations were higher than the interstitial space fluid concentrations at 1 h (1,637 interquartile range, 650, 1,781, vs. 16 mg/l, interquartile range, 7, 86, P & 0.001) and 6 h (48, interquartile range, 17, 93, vs. 4 mg/l, interquartile range, 2, 9, P & 0.001). For intravenous tobramycin, the median epithelial lining fluid concentrations were lower than the interstitial space fluid concentrations at 1 h (0.19, interquartile range, 0.11, 0.31, vs. 18.5 mg/l, interquartile range, 9.8, 23.4, P & 0.001) and 6 h (0.34, interquartile range, 0.2, 0.48, vs. 3.2 mg/l, interquartile range, 0.9, 4.4, P & 0.001). Compared with intravenous tobramycin, nebulized tobramycin achieved higher lung interstitial fluid and epithelial lining fluid concentrations without increasing systemic concentrations.
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.IJANTIMICAG.2010.08.013
Abstract: Pneumonia is a form of lung infection that may be caused by various micro-organisms. The predominant site of infection in pneumonia is debatable. Advances in the fields of diagnostic and therapeutic medicine have had a less than optimal effect on the outcome of pneumonia and one of the many causes is likely to be inadequate antimicrobial concentrations at the site of infection in lung tissue. Traditional antimicrobial therapy guidelines are based on indirect modelling from blood antimicrobial levels. However, studies both in humans and animals have shown the fallacy of this concept in various tissues. Many different methods have been employed to study lung tissue antimicrobial levels with limited success, and each has limitations that diminish their utility. An emerging technique being used to study the pharmacokinetics of antimicrobial agents in lung tissue is microdialysis. Development of microdialysis catheters, along with improvement in analytical techniques, has improved the accuracy of the data. Unfortunately, very few studies have reported the use of microdialysis in lung tissue, and even fewer antimicrobial classes have been studied. These studies generally suggest that this technique is a safe and effective way of assessing the pharmacokinetics of antimicrobial agents in lung tissue. Further descriptive studies need to be conducted to study the pharmacokinetics and pharmacodynamics of different antimicrobial classes in lung tissue. Data emanating from these studies could inform decisions for appropriate dosing schedules of antimicrobial agents in pneumonia.
Publisher: Oxford University Press (OUP)
Date: 21-03-2023
DOI: 10.1093/JBCR/IRAD040
Abstract: Acquired tracheoesophageal fistulae are uncommon in burn patients but can occur as a complication of inhalation injury. We report a case of a 30-yr-old male patient presenting after suffering from inhalation and 25% total body surface area burns. On postburns day 14, he developed a massive tracheoesophageal fistula causing refractory acute respiratory failure. Veno-venous extracorporeal membrane (VV ECMO) oxygenation was initiated without systemic anticoagulation via bi-femoral cannulation under transthoracic echocardiography guidance. He underwent successful 5-hr apnoeic ventilation-assisted surgical repair of the fistula via a right posterolateral thoracotomy. ECMO was discontinued after 36 hr, and he was discharged to the ward after 33 d in the intensive care unit. Inhalation burn injury can cause a delayed life-threatening tracheoesophageal fistula. Surgical repair can be successfully performed for this condition. VV- ECMO can be used to facilitate prolonged apnoeic surgery and to manage refractory respiratory failure due to this condition.
Publisher: Wiley
Date: 02-06-2020
DOI: 10.1002/PHAR.2413
Publisher: American Society for Microbiology
Date: 23-06-2020
DOI: 10.1128/AAC.02584-19
Abstract: Optimal concentrations of unbound antimicrobials are essential for a maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare the effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model. The study design was a prospective, three-phase intervention observational study.
Publisher: Springer Science and Business Media LLC
Date: 07-10-2016
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JTCVS.2012.06.037
Abstract: The study objective was to investigate the effect of renal failure on intermediate-term survival in cardiac surgery patients. All patients aged 18 years or older undergoing coronary artery bypass grafting, valvular surgery, thoracic aortic surgery, or a combination of these from January 1, 2002 to December 1, 2005 were included. Data were obtained from the cardiac surgery and intensive care databases. Using a matching algorithm, the date of death was obtained from the National Death Index. The simplified Medical Diet for Renal Disease formula was used to calculate the estimated glomerular filtration rate, and the patients were stratified accordingly. An estimation of the effect of the preoperative renal function on the interval to death was determined using Cox regression analysis with and without cubic splines and polynomial regression. The long-term survival was described using the Kaplan-Meier product limit method. A total of 5297 patients were included in the present study. The vital status of all patients was obtained at a mean of 2.9 years (range, 1-5) postoperatively. The actuarial 1-year survival rate was 96% ± 1%, and the 3-year survival rate was 92% ± 1%. The greatest early mortality occurred in the severe renal dysfunction group however, the dialysis-dependent renal failure group showed increased mortality over time compared with the other groups. The lowest risk of death (longest interval to death) occurred with an estimated glomerular filtration rate of approximately 90 mL/min/1.73 m(2). The results of our study have shown that preoperative renal dysfunction is an independent predictor of long-term mortality in cardiac surgery patients.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.CMI.2017.03.018
Abstract: Nebulized antibiotics have an established role in patients with cystic fibrosis or bronchiectasis. Their potential benefit to treat respiratory infections in mechanically ventilated patients is receiving increasing interest. In this consensus statement of the European Society of Clinical Microbiology and Infectious Diseases, the body of evidence of the therapeutic utility of aerosolized antibiotics in mechanically ventilated patients was reviewed and resulted in the following recommendations: Vibrating-mesh nebulizers should be preferred to jet or ultrasonic nebulizers. To decrease turbulence and limit circuit and tracheobronchial deposition, we recommend: (a) the use of specifically designed respiratory circuits avoiding sharp angles and characterized by smooth inner surfaces, (b) the use of specific ventilator settings during nebulization including use of a volume controlled mode using constant inspiratory flow, tidal volume 8 mL/kg, respiratory frequency 12 to 15 bpm, inspiratory:expiratory ratio 50%, inspiratory pause 20% and positive end-expiratory pressure 5 to 10 cm H
Publisher: Mary Ann Liebert Inc
Date: 02-2020
Abstract: Hemoptysis and pulmonary embolism (PE) are life-threatening pulmonary emergencies that, when present together, create a therapeutic conundrum. We present an illustrative case of a 65-year-old man with unprovoked submassive PE and moderate hemoptysis due to pulmonary infarction. Hemoptysis precluded systemic anticoagulation. Failing a conservative management strategy, we administered nebulized tranexamic acid. After four doses of nebulized tranexamic acid 500 mg, 6 hours apart, hemoptysis had ceased. Systemic anticoagulation with intravenous heparin was then successfully commenced 12 hours after the last episode of hemoptysis. The patient was weaned off high-flow nasal oxygen therapy over the course of the next 5 days with no hemoptysis recurrence. Noting the absence of trial evidence, but good pharmacological rationale and our positive experience, we suggest tranexamic acid is a useful noninvasive treatment option for the management of such conditions. Consent for this publication was obtained from the patient.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Walter de Gruyter GmbH
Date: 12-11-2020
Abstract: The aim of our work was to develop and validate a hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass spectrometry (HILIC-ESI-MS/MS) methods for the quantification of tobramycin (TMC) and lincomycin (LMC)in plasma, microdialysis fluid and urine. Protein precipitation was used to extract TMC and LMC from plasma, while microdialysis fluid and urine s le were diluted prior to instrumental analysis. Mobile phase A consisted of 2 mM ammonium acetate in 10% acetonitrile with 0.2% formic acid (v/v) and mobile phase B consisted of 2 mM ammonium acetate in 90% acetonitrile with 0.2% formic acid (v/v). Gradient separation (80%–10% of mobile phase B) for TMC was done using a SeQuant zic-HILIC analytical guard column. While separation of LMC was performed using gradient elution (100%–40% of mobile phase B) on a SeQuant zic-HILIC analytical column equipped with a SeQuant zic-HILIC guard column. Vancomycin (VCM) was used as an internal standard. A quadratic calibration was obtained over the concentration range for plasma of 0.1–20 mg/L for TMC and 0.05–20 mg/L for LMC, for microdialysis fluid of 0.1–20 mg/L for both TMC and LMC, and 1–100 mg/L for urine for both TMC and LMC. For TMS and LMC, validation testing for matrix effects, precision and accuracy, specificity and stability were all within acceptance criteria of ±15%. The methods described here meet validation acceptance criteria and were suitable for application in a pilot pharmacokinetic research study performed in a sheep model.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.IJANTIMICAG.2021.106431
Abstract: Extracorporeal membrane oxygenation (ECMO) can affect antimicrobial pharmacokinetics. This case report describes a 33-year-old male with newly diagnosed acquired immunodeficiency syndrome presenting in acute severe type 1 respiratory failure. On investigation, the patient had positive cultures for Candida albicans from respiratory specimens and high blood cytomegalovirus titres, and required venovenous ECMO therapy for refractory respiratory failure. Intravenous fluconazole (6 mg/kg, 24-h) and ganciclovir (5 mg/kg, 12-h) was commenced. Pre-oxygenator, post-oxygenator and arterial blood s les were collected after antibiotic administration, and were analysed for total fluconazole and ganciclovir concentrations. Although there was a 40% increase in the volume of distribution for fluconazole relative to healthy volunteers, the pharmacodynamic targets for prophylaxis were still met. The area under the curve exposure of ganciclovir (50.78 mg•h/L) achieved target thresholds. The ECMO circuit had no appreciable effect on achievement of therapeutic exposures of fluconazole and ganciclovir.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2020
DOI: 10.1186/S13104-020-05259-Z
Abstract: The advent of new technologies has made it possible to explore alternative ventilator manufacturing to meet the worldwide shortfall for mechanical ventilators especially in pandemics. We describe a method using rapid prototyping technologies to create an electro-mechanical ventilator in a cost effective, timely manner and provide results of testing using an in vitro–in vivo testing model. Rapid prototyping technologies (3D printing and 2D cutting) were used to create a modular ventilator. The artificial manual breathing unit (AMBU) bag connected to wall oxygen source using a flow meter was used as air reservoir. Controlled variables include respiratory rate, tidal volume and inspiratory: expiratory (I:E) ratio. In vitro testing and In vivo testing in the pig model demonstrated comparable mechanical efficiency of the test ventilator to that of standard ventilator but showed the material limits of 3D printed gears. Improved gear design resulted in better ventilator durability whilst reducing manufacturing time ( 2-h). The entire cost of manufacture of ventilator was estimated at 300 Australian dollars. A cost-effective novel rapid prototyped ventilator for use in patients with respiratory failure was developed in 2-h and was effective in anesthetized, healthy pig model.
No related grants have been discovered for Jayesh Dhanani.