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2.
Anaesthesia ; 2022 Mar 23.
Article En | MEDLINE | ID: mdl-35319088

Respiratory adverse events in adults with COVID-19 undergoing general anaesthesia can be life-threatening. However, there remains a knowledge gap about respiratory adverse events in children with COVID-19. We created an international observational registry to collect airway management outcomes in children with COVID-19 who were having a general anaesthetic. We hypothesised that children with confirmed or suspected COVID-19 would experience more hypoxaemia and complications than those without. Between 3 April 2020 and 1 November 2020, 78 international centres participated. In phase 1, centres collected outcomes on all children (age ≤ 18 y) having a general anaesthetic for 2 consecutive weeks. In phase 2, centres recorded outcomes for children with test-confirmed or suspected COVID-19 (based on symptoms) having a general anaesthetic. We did not study children whose tracheas were already intubated. The primary outcome was the incidence of hypoxaemia during airway management. Secondary outcomes included: incidence of other complications; and first-pass success rate for tracheal intubation. In total, 7896 children were analysed (7567 COVID-19 negative and 329 confirmed or presumed COVID-19 positive). The incidence of hypoxaemia during airway management was greater in children who were COVID-19 positive (24 out of 329 (7%) vs. 214 out of 7567 (3%); OR 2.70 (95%CI 1.70-4.10)). Children who had symptoms of COVID-19 had a higher incidence of hypoxaemia compared with those who were asymptomatic (9 out of 51 (19%) vs. 14 out of 258 (5%), respectively; OR 3.7 (95%CI 1.5-9.1)). Children with confirmed or presumed COVID-19 have an increased risk of hypoxaemia during airway management in conjunction with general anaesthesia.

3.
Anaesthesia ; 77(4): 438-448, 2022 04.
Article En | MEDLINE | ID: mdl-35083739

Tramadol is a bitter atypical opioid analgesic drug and is prescribed to treat postoperative pain in children. However, in many countries there is no licensed paediatric tramadol formulation available. We have formulated a novel chewable chocolate-based drug delivery system for the administration of tramadol to children. This pilot, single-centre, open-label, randomised clinical study assessed the taste tolerability and comparative population pharmacokinetics of the novel tramadol chewable tablet against a compounded tramadol hydrochloride oral liquid, at a dose of 1 mg.kg-1 . A 5-point facial hedonic scale was used by the children, parents and nurses to assess tolerability. One hundred and forty-one children aged 3-16 years were given tramadol 30 min before general anaesthesia. Blood samples were taken following the induction of anaesthesia and for up to 5 h following tramadol administration. Tramadol and its active metabolite O-desmethyltramadol were analysed using reversed-phase high-performance liquid chromatography. A population pharmacokinetic model was built using non-linear mixed effects modelling. The relative bioavailability for the tablet was 1.25 times higher (95%CI 1.16-1.35) than for tramadol hydrochloride oral liquid, while the absorption rate constant for the tablet was significantly lower (1.97 h-1 vs. 3.34 h-1 , p < 0.001). Larger inter-individual variability in absorption rates were observed with the liquid tramadol. The tramadol chewable tablet was more acceptable in taste to children when assessed by the children, parents and nurses (all p < 0.001). We conclude that the novel tramadol chewable tablet has favourable acceptability and more reliable relative bioavailability in children compared with tramadol hydrochloride oral liquid.


Chocolate , Tramadol , Administration, Oral , Adolescent , Analgesics, Opioid , Child , Child, Preschool , Humans , Tablets , Tramadol/pharmacokinetics
4.
Article En | MEDLINE | ID: mdl-34649173

Multimodal analgesia is employed in paediatric pain management to maximise analgesia and minimise side effects. Tramadol is dosed at 1-1.5 mg/kg to treat severe pain in children but the assay for tramadol in plasma samples for pharmacokinetic and toxicology studies does not often consider concurrently administered medications. In this study we developed and validated an HPLC-UV method to quantify tramadol and its main metabolite (O-desmethyltramadol) in human plasma in the presence of seven potentially interfering drugs. Sample preparation method was developed by combining liquid-liquid extraction and protein precipitation. Chromatographic separation was achieved on a BDS-Hypersil-C18 column (5 µm, 250 × 4.6 mm) using a double gradient method. The limit of quantification was 6.7 ng/ml for both tramadol and ODT. The precision and accuracy were in compliance with ICH guidelines. This method was successfully employed to analyse the blood samples of 137 paediatric participants in a tramadol pharmacokinetic trial.


Chromatography, High Pressure Liquid/methods , Tramadol/analogs & derivatives , Tramadol/blood , Adult , Child , Humans , Limit of Detection , Linear Models , Reproducibility of Results , Spectrophotometry, Ultraviolet , Tramadol/chemistry , Tramadol/pharmacokinetics
5.
Anaesthesia ; 76(1): 91-100, 2021 01.
Article En | MEDLINE | ID: mdl-32932556

For healthcare workers performing aerosol-generating procedures during the COVID-19 pandemic, well fitted filtering facepiece respirators, for example, N95/FFP2 or N99/FFP3 masks, are recommended as part of personal protective equipment. In this review, we evaluate the role of fit checking and fit testing of respirators, in addition to airborne protection provided by respirators. Filtering facepiece respirators are made of material with sufficient high filter capacity to protect against airborne respiratory viruses. Adequate viral protection can only be provided by respirators that properly fit the wearer's facial characteristics. Initial fit pass rates vary between 40% and 90% and are especially low in female and in Asian healthcare workers. Fit testing is recommended to ensure a proper fit of respirators for the individual healthcare worker so that alternative respirators can be selected if required. Although fit testing is required to comply with respirator standards, it is not performed consistently within all healthcare settings. Fit checking (a self-test) is recommended every time a healthcare worker dons a respirator, but is unreliable in detecting proper fit or leak. Additionally, fit testing has a high educational value and as such is best performed as part of a hospital respiratory protection programme. Whether fit checking alone, as opposed to fit tested and fit checked respirators, provides adequate airborne protection against aerosols containing the SARS-CoV-2 virus and other respiratory viruses remains unknown. While fit testing undoubtedly incurs additional costs, it is still recommended, not only to protect healthcare workers but also as it may reduce overall healthcare cost when considering the potential costs of sickness leave and the associated legal costs of compensation.


COVID-19/prevention & control , Masks/standards , Personal Protective Equipment/standards , Humans , N95 Respirators , Pandemics , Respiratory Protective Devices/standards
6.
Anaesthesia ; 75(10): 1364-1371, 2020 10.
Article En | MEDLINE | ID: mdl-32534465

The COVID-19 pandemic marks an extraordinary global public health crisis unseen in the last century, with its rapid spread worldwide and associated mortality burden. The longevity of the crisis and disruption to normality is unknown. With COVID-19 set to be a chronic health crisis, clinicians will be required to maintain a state of high alert for an extended period. The support received before and during an incident is likely to influence whether clinicians experience psychological growth or injury. An abundance of information is emerging on disease epidemiology, pathogenesis and infection control prevention. However, literature on interventions for supporting the psychological well-being of healthcare workers during disease outbreaks is limited. This article summarises the available management strategies to increase resilience in healthcare workers during the COVID-19 pandemic and beyond. It focuses on self-care and organisational justice. It highlights various individual as well as organisational strategies. With the success of slowing disease spread in many countries to date, and reduced work-load due to limitations on elective surgery in many institutions, there is more time and opportunity to be pro-active in implementing measures to mitigate or minimise potential adverse psychological effects and improve, restore and preserve the well-being of the workforce now and for years to come. The purpose of this review is to review available literature on strategies for minimising the psychological impact of the COVID-19 pandemic on clinicians and to identify pro-active holistic approaches which may be beneficial for healthcare workers both for the current crisis and into the future.


Betacoronavirus , Coronavirus Infections/epidemiology , Health Personnel/psychology , Pneumonia, Viral/epidemiology , Psychological Distress , Resilience, Psychological , COVID-19 , Humans , Pandemics , SARS-CoV-2
7.
Anaesthesia ; 75(11): 1461-1468, 2020 11.
Article En | MEDLINE | ID: mdl-32533791

Children may develop changes in their behaviour following general anaesthesia. Some examples of negative behaviour include temper tantrums and nightmares, as well as sleep and eating disorders. The aim of this study was to determine whether dexmedetomidine reduces the incidence of negative behaviour change after anaesthesia for day case surgery in children aged two to seven years. Children were randomly allocated to one of three groups: a premedication group received 2 mg.kg-1 intranasal dexmedetomidine; an intra-operative group received 1 mg.kg-1 intravenous dexmedetomidine; and a control group. The primary outcome was the incidence of negative behaviour on postoperative day 3 using the Post-Hospitalisation Behaviour Questionnaire for Ambulatory Surgery (PHBQ-AS) and the Strength and Difficulties Questionnaire (SDQ). Secondary outcomes included: the incidence of negative behaviour on postoperative days 14 and 28; anxiety at induction; emergence delirium; pain; length of recovery and hospital stay; and any adverse events. The data for 247 patients were analysed. Negative behaviour change on postoperative day 3 was similar between all three groups when measured with the PHBQ-AS (47%, 44% and 51% respectively; adjusted p=0.99) and the SDQ (median scores 7.5, 6.0 and 8.0 respectively; adjusted p=0.99). The incidence of negative behaviour in the group who received dexmedetomidine intra-operatively was less at postoperative day 28 (15% compared with 36% in the dexmedetomidine premedication group and 41% in the control group, p<0.001). We conclude that dexmedetomidine does not reduce the incidence of negative behaviour on postoperative day 3 in two to seven-year olds having day case procedures.


Child Behavior/drug effects , Dexmedetomidine/pharmacology , Hypnotics and Sedatives/pharmacology , Intraoperative Care/methods , Postoperative Complications/prevention & control , Premedication/methods , Ambulatory Surgical Procedures , Child , Child, Preschool , Dexmedetomidine/administration & dosage , Dexmedetomidine/therapeutic use , Double-Blind Method , Female , Humans , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/therapeutic use , Male , Surveys and Questionnaires
8.
Anaesthesia ; 74(10): 1252-1259, 2019 10.
Article En | MEDLINE | ID: mdl-31077340

Propofol is the most commonly administered intravenous agent for anaesthesia in children. However, there are concerns that the emulsified preparation may not be safe in children with an allergy to egg, peanut, soybean or other legumes. We conducted a retrospective study of children with immunologically confirmed egg, peanut, soybean or legume allergy and who underwent general anaesthesia at Princess Margaret Hospital for Children between 2005 and 2015. We extracted details regarding allergy diagnosis, each anaesthetic administered and any adverse events or signs of an allergic reaction in the peri-operative period. A convenience sample of patients without any known food allergies was identified from our prospective anaesthesia research database and acted as a control group. We identified 304 food-allergic children and 649 procedures where propofol was administered. Of these, 201 (66%) had an egg allergy, 226 (74%) had a peanut allergy, 28 (9%) had a soybean allergy and 12 (4%) had a legume allergy. These were compared with 892 allergy-free patients who were exposed to propofol. In 10 (3%) allergy patients and 124 (14%) allergy-free patients, criteria for a possible allergic reaction were met. In nine of the food-allergic children and in all the controls valid non-allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a child with a previous history of intralipid allergy. We conclude that genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.


Anesthetics, Intravenous/adverse effects , Food Hypersensitivity/complications , Propofol/adverse effects , Adolescent , Anesthesia, General , Child , Child, Preschool , Drug Hypersensitivity/etiology , Egg Hypersensitivity/complications , Emulsions/adverse effects , Fabaceae/adverse effects , Female , Humans , Infant , Infant, Newborn , Male , Peanut Hypersensitivity/complications , Phospholipids/adverse effects , Retrospective Studies , Soybean Oil/adverse effects , Glycine max/adverse effects
9.
Anaesthesia ; 73(12): 1469-1477, 2018 Dec.
Article En | MEDLINE | ID: mdl-29984832

Midazolam is one of many bitter drugs where provision of a suitable oral paediatric formulation, particularly in the pre-anaesthetic setting, remains a challenge. To overcome this problem, a novel chocolate-based tablet formulation has been developed with positive pre-clinical results. To further investigate the potential of this formulation, 150 children aged 3-16 years who were prescribed midazolam as a premedication were randomly assigned to receive 0.5 mg.kg-1 either as the novel formulation or an intravenous solution given orally, which is the current standard at our institution. Tolerability was assessed by each child, parent and nurse using a 5-point facial hedonic scale and efficacy was determined as the time to onset of sedation. Blood samples for midazolam and 1-hydroxymidazolam levels were analysed using high-performance liquid chromatography. Population pharmacokinetics were evaluated using non-linear mixed effects modelling. The novel formulation had significantly improved tolerability scores from children, parents and nurses (all p < 0.001). Time to effect was not different between the groups (p = 0.140). The pharmacokinetics of midazolam and 1-hydroxymidazolam were able to be modelled simultaneously. The novel formulation was subject to a higher estimated first-pass metabolism compared with the intravenous solution (8.6% vs. 5.0%) and a significantly lower relative bioavailability of 82.1% (p = 0.013), with no other significant differences. Exposure relative to dose was in the range previously reported for midazolam syrup. We conclude that the novel chocolate-based formulation of midazolam provides improved tolerability while remaining efficacious with suitable pharmacokinetics when used as a premedicant for children.


Hypnotics and Sedatives/adverse effects , Hypnotics and Sedatives/pharmacokinetics , Midazolam/adverse effects , Midazolam/pharmacokinetics , Preanesthetic Medication , Administration, Oral , Biotransformation , Child , Child, Preschool , Chocolate , Drug Compounding , Female , Humans , Infant , Male , Midazolam/analogs & derivatives , Nurses , Parents , Patient Safety , Prospective Studies , Single-Blind Method , Taste
10.
Br J Anaesth ; 120(3): 571-580, 2018 Mar.
Article En | MEDLINE | ID: mdl-29452814

BACKGROUND: Laryngeal mask airways (LMA) are widely used during tonsillectomies. Contrasting evidence exists regarding the timing of the removal and the risk of perioperative respiratory adverse events. We assessed whether the likelihood of perioperative respiratory adverse events is influenced by the timing of LMA removal in children with at least one risk factor for these events. METHODS: Participants (n=290, 0-16 yr) were randomised to have their LMA removed either deep (in theatre by anaesthetist at end-tidal sevoflurane >1 minimum alveolar concentration) or awake (in theatre by anaesthetist or in postanaesthesia care unit by anaesthetist or trained nurse). The primary outcome was the occurrence of perioperative respiratory adverse events over the whole emergence and postanaesthesia care unit phases of anaesthesia. The secondary outcome was the occurrence of perioperative respiratory adverse events over the distinct phases of emergence and postanaesthesia care unit. RESULTS: Data from 283 participants were analysed. PRIMARY OUTCOME: even though a higher occurrence of adverse events was observed in the awake group, no evidence for a difference was found [45% vs 35%, odds ratio (OR): 1.5, 95% confidence interval (CI): 0.9-2.5, P=0.09]. Secondary outcome: there was no evidence for a difference between the groups during emergence [19 (14%) deep vs 25 (18%) awake, OR: 0.74, 95%CI: 0.39-1.42, P=0.37]. However, in the postanaesthesia care unit, children with an awake rather than deep removal experienced significantly more adverse events [55 (39%) vs 37 (26%); OR: 1.85, 95%CI: 1.12-3.07, P=0.02]. CONCLUSION: We found no evidence for a difference in the timing of the LMA removal on the incidence of respiratory adverse events over the whole emergence and postanaesthesia care unit phases. However, in the postanaesthesia care unit solely, awake removal was associated with significantly more respiratory adverse events than deep removal. TRIAL REGISTRATION NUMBER: ACTRN12609000387224 (www.anzctr.org.au).


Anesthesia Recovery Period , Laryngeal Masks , Respiration Disorders/epidemiology , Tonsillectomy , Wakefulness , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Prospective Studies , Risk , Western Australia/epidemiology
11.
Anaesthesia ; 73(2): 160-168, 2018 02.
Article En | MEDLINE | ID: mdl-29168575

Cuffed tracheal tubes are increasingly used in paediatric anaesthetic practice. This study compared tidal volume and leakage around cuffed and uncuffed tracheal tubes in children who required standardised mechanical ventilation of their lungs in the operating theatre. Children (0-16 years) undergoing elective surgery requiring tracheal intubation were randomly assigned to receive either a cuffed or an uncuffed tracheal tube. Assessments were made at five different time-points: during volume-controlled ventilation 6 ml.kg-1 , PEEP 5 cmH2 O and during pressure-controlled ventilation 10 cmH2 O / PEEP 5 cmH2 O. The pressure-controlled ventilation measurement time-points were: just before a standardised recruitment manoeuvre; just after recruitment manoeuvre; 10 min; and 30 min after the recruitment manoeuvre. Problems and complications were recorded. During volume-controlled ventilation, leakage was significantly less with cuffed tracheal tubes than with uncuffed tracheal tubes; in ml.kg-1 , median (IQR [range]) 0.20 (0.13-0.39 [0.04-0.60]) vs. 0.82 (0.58-1.38 [0.24-4.85]), respectively, p < 0.001. With pressure-controlled ventilation, leakage was less with cuffed tracheal tubes and stayed unchanged over a 30-min period, whereas with uncuffed tracheal tubes, leakage was higher and increased further over the 30-min period. Tidal volumes were higher in the cuffed group and increased over time, but in the uncuffed group were lower and decreased over time. Both groups showed an increase in tidal volumes following recruitment manoeuvres. There were more short-term complications with uncuffed tracheal tubes, but no major complications were recorded in either group at long-term follow-up. With standardised ventilator settings, cuffed tracheal tubes produced better ventilation characteristics compared with uncuffed tracheal tubes during general anaesthesia for routine elective surgery.


Intubation, Intratracheal/instrumentation , Adolescent , Airway Management/instrumentation , Airway Management/methods , Child , Child, Preschool , Equipment Design , Female , Humans , Incidence , Infant , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/methods , Male , Oxygen/blood , Postoperative Complications/epidemiology , Respiration, Artificial/adverse effects , Respiration, Artificial/instrumentation , Respiration, Artificial/methods , Tidal Volume
12.
Br J Anaesth ; 119(5): 979-983, 2017 Nov 01.
Article En | MEDLINE | ID: mdl-29028932

BACKGROUND: Surgical Pleth Index (SPI) is a non-invasive, dimensionless score (0-100) aimed to allow an estimate of intraoperative nociception. Thus, it may be a useful tool to guide intraoperative analgesia. However, no optimum SPI target range for the use in children has yet been defined. It was the aim of this study to define a clinically appropriate SPI target to predict moderate-severe postoperative pain in children. METHODS: After ethics approval 105 children (2-16 yr) undergoing elective sevoflurane/opioid-based anaesthesia were included. SPI was recorded directly before the end of surgery and compared with acute postoperative pain (age appropriately assessed on different pain scales in the age groups two to three yr, four to eight yr and nine to16 yr) in the postoperative acute care unit (PACU). RESULTS: Data of 93 children were analysed. A significant negative correlation was found between age and SPI (r=-0.43; P=0.03). The SPI cut-off value with the highest sensitivity (76%) and specificity (62%) in all children combined was 40. The negative predictive value for SPI ≤ 40 to predict the absence of moderate-severe pain in PACU was 87.5%. The commonly used SPI cut-off (50) published in all related studies had neither any clinically relevant sensitivity nor specificity to predict the presence or absence of acute pain in PACU. CONCLUSIONS: The results suggest that a lower (≤ 40) than previously published (50) target for SPI may be more appropriate in studies investigating SPI guided anaesthesia in children, if the avoidance of moderate-severe postoperative pain is the main goal. CLINICAL TRIAL REGISTRATION: ACTRN12616001139460.


Monitoring, Intraoperative/methods , Nociception/drug effects , Pain, Postoperative/diagnosis , Adolescent , Age Factors , Child , Child, Preschool , Female , Humans , Male , Predictive Value of Tests , Sensitivity and Specificity
13.
Br J Anaesth ; 119(3): 532-540, 2017 Sep 01.
Article En | MEDLINE | ID: mdl-28969309

BACKGROUND: The anaesthetic dose causing neurotoxicity in animals has been evaluated, but the relationship between duration of volatile anaesthetic (VA) exposure and neurodevelopment in children remains unclear. METHODS: Data were obtained from the Western Australian Pregnancy Cohort (Raine) Study, with language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E] and Total [CELF-T]) and cognition (Coloured Progressive Matrices [CPM]) assessed at age 10 yr. Medical records were reviewed, and children divided into quartiles based on total VA exposure duration before age three yr. The association between test score and exposure duration quartile was evaluated using linear regression, adjusting for patient characteristics and comorbidity. RESULTS: Of 1622 children with available test scores, 148 had documented VA exposure and were split into the following quartiles: ≤25, >25 to ≤35, >35 to ≤60 and >60 min. Compared with unexposed children, CELF-T scores for children in the first and second quartiles did not differ, but those in the third and fourth quartiles had significantly lower scores ([3 rd quartile - Unexposed] -5.3; 95% confidence interval [CI], (-10.2 - -0.4), [4 th quartile - Unexposed] -6.2; 95% CI, (-11.6 - -0.9). CELF-E showed similar findings, but significant differences were not found in CELF-R or CPM for any quartile. CONCLUSIONS: Children with VA exposures ≤35 min did not differ from unexposed children, but those with exposures >35 min had lower total and expressive language scores. It remains unclear if this is a dose-response relationship, or if children requiring longer exposures for longer surgeries have other clinical reasons for lower scores.


Anesthetics, General/adverse effects , Cognition Disorders/chemically induced , Language Disorders/chemically induced , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Neuropsychological Tests , Retrospective Studies , Time Factors , Western Australia , Young Adult
14.
Br J Anaesth ; 119(1): 150-157, 2017 Jul 01.
Article En | MEDLINE | ID: mdl-28974069

BACKGROUND: Perioperative respiratory adverse events (PRAE) remain the leading cause of morbidity and mortality in the paediatric population. This double-blinded randomized control trial investigated whether inhaled salbutamol premedication decreased the occurrence of PRAE in children identified as being at high risk of PRAE. METHODS: Children with at least two parentally reported risk factors for PRAE undergoing elective surgery were eligible for recruitment. They were randomized to receive either salbutamol (200 µg) or placebo prior to their surgery and PRAE (bronchospasm, laryngospasm, airway obstruction, desaturation, coughing and stridor) were recorded. RESULTS: Out of 470 children (6-16 yr, 277 males, 59%) recruited, 462 were available for an intention-to-treat analysis. Thirty-two (14%) and 27 (12%) children from the placebo and salbutamol groups experienced PRAE. This difference was not significant [odds ratio (OR): 0.83, 95% confidence interval (CI): 0.48-1.44, P : 0.51]. Oxygen desaturation [14/232 (6%) vs 14/230 (6%), OR: 1.01, 95% CI: 0.47-2.17, P : 0.98] and severe coughing [12/232 (5%) vs 10/230 (4%), OR: 0.83, 95% CI: 0.35-1.97, P : 0.68] were the most common PRAE, but did not significantly differ between the groups. The occurrence of PRAE was slightly lower in children with respiratory symptoms who received salbutamol compared with placebo [16/134 (12%) vs 21/142 (15%), OR: 0.93, 95% CI: 0.38-2.26, P : 0.87], but was not significantly different. CONCLUSIONS: Premedication with salbutamol to children aged between 6 and 16 years and at high risk of PRAE prior to their surgery did not reduce their risk of PRAE. TRIAL REGISTRATION NUMBER: ACTRN12612000626864 ( www.anzctr.org.au ).


Adrenergic beta-2 Receptor Agonists/therapeutic use , Albuterol/therapeutic use , Premedication , Respiration Disorders/prevention & control , Adolescent , Child , Double-Blind Method , Female , Humans , Laryngeal Masks , Male , Perioperative Period , Risk
15.
Anaesthesia ; 72(11): 1388-1397, 2017 Nov.
Article En | MEDLINE | ID: mdl-28872662

Inhalation of aerosolised medications are the mainstay of treatment for a number of chronic lung diseases and have several advantages over systemically-administered medications. These include more rapid onset of action for drugs such as ß-adrenergic agonists when compared with oral medication, high luminal doses for inhaled antibiotics when used to treat endobronchial infection, and an improved therapeutic index compared with systemic delivery for these and other classes of drugs such as corticosteroids. The use of aerosolised drugs to treat patients whose tracheas are intubated is less well established, in part because systemic delivery via the intravenous route can be a simpler alternative for many drugs. Consequently, research in this area is largely limited to a number of in vitro studies and very few clinical trials. Unfortunately, a lack of focus in this area has resulted in a number of practices which at best are ineffective, and at worst dangerous for the patient. Although there have been some attempts to re-invigorate research in order to improve delivery systems, current devices are, to a great extent, based on long-standing technology developed more than 50 years ago. In this review, we explore current knowledge and provide guidance as to when and how the inhaled route may be of value when treating patients whose tracheas are intubated, and we set out the challenges facing those attempting to advance the topic. We conclude by reviewing current areas of interest that may lead to more effective and widespread use of aerosols in the treatment of intubated patients.


Aerosols , Noninvasive Ventilation/methods , Pharmaceutical Preparations/administration & dosage , Respiration, Artificial/methods , Administration, Inhalation , Adolescent , Child , Child, Preschool , Humans , Infant , Nebulizers and Vaporizers
16.
Anesth Analg ; 125(3): 837-845, 2017 09.
Article En | MEDLINE | ID: mdl-28489641

BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. METHODS: A total of 722 infants ≤60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born at <26 weeks of gestation. Moderate hypotension was defined as mean arterial pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The primary outcome was any measured hypotension <35 mm Hg from start of anesthesia to leaving the operating room. This analysis is reported primarily as intention to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA compared with RA predicting any measured hypotension of <35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (confidence interval [CI], 2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and 16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable modeling, group assignment (GA versus RA), weight at the time of surgery, and minimal intraoperative temperature were risk factors for hypotension. Interventions for hypotension occurred more commonly in the GA group compared with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA reduces the incidence of hypotension and the chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.


Anesthesia, Conduction/adverse effects , Anesthesia, General/adverse effects , Blood Pressure/drug effects , Hypotension/chemically induced , Hypotension/epidemiology , Wakefulness/drug effects , Anesthesia, Conduction/trends , Anesthesia, General/trends , Blood Pressure/physiology , Child, Preschool , Humans , Hypotension/diagnosis , Infant , Infant, Newborn , Prospective Studies , Wakefulness/physiology
18.
Br J Anaesth ; 117(2): 151-63, 2016 08.
Article En | MEDLINE | ID: mdl-27440626

Respiratory adverse events are one of the major causes of morbidity and mortality in paediatric anaesthesia. Aside from predisposing conditions associated with an increased risk of respiratory incidents in children such as concurrent infections and chronic airway irritation, there are adverse respiratory events directly attributable to the impact of anaesthesia on the respiratory system. Anaesthesia can negatively affect respiratory drive, ventilation/perfusion (V/Q) matching and tidal breathing, all resulting in potentially devastating hypoxaemia. Understanding paediatric respiratory physiology and its changes during anaesthesia will enable anaesthetists to anticipate, recognize and prevent deterioration that can lead to respiratory failure. This review aims to give a comprehensive overview of the effects of anaesthesia on respiration in children. It focuses on the impact of the different components of anaesthesia, patient positioning and procedure-related changes on respiratory physiology.


Anesthesia , Anesthesiology , Child , Humans , Respiration , Respiration, Artificial , Respiratory Insufficiency
19.
Anaesthesia ; 70(12): 1412-7, 2015 Dec.
Article En | MEDLINE | ID: mdl-26355492

Many studies comparing the i-gel(™) with laryngeal masks include patients in whom laryngeal mask cuff inflation pressures are higher than recommended, or involve the use of neuromuscular blocking drugs and positive pressure ventilation. We compared the i-gel with the PRO-Breathe(®) laryngeal mask in anaesthetised, spontaneously breathing children. Two hundred patients aged up to 16 years were randomly allocated to either the i-gel or the PRO-Breathe laryngeal mask. The PRO-Breathe was inflated to an intracuff pressure of 40 cmH2 O. All patients received pressure support of 10 cmH2 O and positive end-expiratory pressure of 5 cmH2 O. Successful insertion at the first attempt was 82% for the i-gel compared with 93% for the PRO-Breathe (p = 0.019). Leakage volume was significantly higher with i-gel sizes 1.5 (p = 0.015), 2 (p = 0.375), 2.5 (p = 0.021) and 3 (p = 0.003) compared with the equivalent-sized PRO-Breathe device. Device dislodgement following successful initial placement was more frequent with the i-gel (5%) compared with the PRO-Breathe laryngeal mask (0%). We conclude that the PRO-Breathe laryngeal mask is superior to the i-gel in terms of leakage volume and device dislodgement.


Laryngeal Masks , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Positive-Pressure Respiration
20.
Anaesthesia ; 70(10): 1160-4, 2015 Oct.
Article En | MEDLINE | ID: mdl-26032864

Increased levels of exhaled nitric oxide (eNO) may be a more objective predictor in identifying children at higher risk of peri-operative adverse respiratory events than the presence of risk factors such as recent cold or wheeze. Children with either none or ≥ 2 risk factors had eNO measured before surgery and any peri-operative adverse respiratory events were recorded. We found that an elevated eNO level was only predictive of adverse respiratory events in children with ≥ 2 risk factors (OR 2.96 (95% CI 1.48-5.93), p = 0.002). The presence of risk factors had a better predictive capability than a raised eNO level (OR 3.83 (95% CI 1.85-7.95), p < 0.001). The combination of both predictors did not improve the predictive capability for adverse respiratory events (OR 1.93 (95% CI 1.44-2.59), p < 0.001). We conclude that measuring eNO levels does not lead to improved prediction of adverse respiratory events and that, in routine clinical practice, an accurate history of risk factors remains the most appropriate tool for successfully identifying children at risk of peri-operative adverse respiratory events.


Nitric Oxide/analysis , Postoperative Complications , Preoperative Care/methods , Respiration Disorders/etiology , Adolescent , Anesthesia, General/adverse effects , Anesthesia, General/methods , Biomarkers/analysis , Breath Tests/methods , Case-Control Studies , Child , Child, Preschool , Female , Humans , Male , Minor Surgical Procedures , Predictive Value of Tests
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