Magnesium sulphate intravenously reduces tachycardia side-effects of ß2-agonists.

Intravenous magnesium sulphate allows safer intravenous ß2-agonist delivery in acute-severe and life-threatening asthma attacks https://bit.ly/3veUpfC.

Safety and efficacy of tetrastarches in surgery and trauma: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Hydroxyethyl starch (HES) 130 is a frequently used fluid to replace intravascular losses during surgery or trauma. In the past years, several trials performed in critically ill patients have raised questions regarding the safety of this product. Our aim in this meta-analysis was to evaluate the safety and efficacy of 6% HES during surgery and in trauma. METHODS: This systematic review and meta-analysis was registered at PROSPERO (CRD42018100379). We included 85 fully published articles from 1980 to June 2018 according to the protocol and three additional recent articles up to June 2020 in English, French, German, and Spanish reporting on prospective, randomised, and controlled clinical trials applying volume therapy with HES 130/0.4 or HES 130/0.42, including combinations with crystalloids, to patients undergoing surgery. Comparators were albumin, gelatin, and crystalloids only. A meta-analysis could not be performed for the two trauma studies as there was only one study that reported data on endpoints of interest. RESULTS: Surgical patients treated with HES had lower postoperative serum creatinine (P<0.001) and showed no differences in renal dysfunction, renal failure, or renal replacement therapy. Although there was practically no further difference in the colloids albumin or gelatin, the use of HES improved haemodynamic stability, reduced need for vasopressors (P<0.001), and decreased length of hospital stay (P<0.001) compared with the use of crystalloids alone. CONCLUSIONS: HES was shown to be safe and efficacious in the perioperative setting. Results of the present meta-analysis suggest that when used with adequate indication, a combination of intravenous fluid therapy with crystalloids and volume replacement with HES as colloid has clinically beneficial effects over using crystalloids only.

Achieving proficiency in rigid bronchoscopy-a study in manikins.

BACKGROUND: Rigid bronchoscopy may be used to relieve acute airway obstruction following induction of anaesthesia and is a recommended option for management of the difficult airway. The ability of anaesthetists to perform rigid bronchoscopy has not been reported. We sought to explore the acquisition of procedural skill in rigid bronchoscopy by anaesthesiologists in a manikin. METHODS: In a prospective interventional study, participants were asked to perform 40 rigid bronchoscopies in a TruCorp AirSim Advance airway manikin, configured to a randomised sequence of easy or difficult laryngoscopic grades to which the participants were blinded. The primary outcome was stabilisation (the attempt after which no further reduction in procedural time occurred). Dental injury and oesophageal intubation were also recorded. Forty anaesthesiologists and 40 unskilled controls (without laryngoscopic skills) participated. RESULTS: In the easy model, stabilisation occurred at attempt 8 in the anaesthesiology group and 10 in the unskilled controls. In the difficult model, stabilisation occurred at attempt 10 in both groups. Dental injury was less common in the anaesthesiology group. The proportion of participants achieving procedural competency did not differ between groups in either the easy (35/40 vs. 30/40) or difficult model (32/40 vs. 25/40). CONCLUSIONS: This study shows that the technical skill of rigid bronchoscopy can be acquired within 10 repetitions in a manikin model. As procedural competence and complication frequency vary with the laryngoscopic grade of the model, both easy and difficult configurations should be used for training. Advanced laryngoscopic skills are not required prior to training in this technique.

Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures: a Cochrane systematic review.

BACKGROUND: Buffered intravenous fluid preparations contain substrates to maintain acid-base status. The objective of this systematic review was to compare the effects of buffered and non-buffered fluids administered during the perioperative period on clinical and biochemical outcomes. METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library until May 2017 and included all randomised controlled trials that evaluated buffered versus non-buffered fluids, whether crystalloid or colloid, administered to surgical patients. We assessed the selected studies for risk of bias and graded the level of evidence in accordance with Cochrane recommendations. RESULTS: We identified 19 publications of 18 randomised controlled trials, totalling 1096 participants. Mean difference (MD) in postoperative pH was 0.05 units lower immediately following surgery in the non-buffered group (12 studies of 720 participants; 95% confidence interval (CI) 0.04 to 0.07; I 2 = 61%). This difference did not persist on postoperative day 1. Serum chloride concentration was higher in the non-buffered group at the end of surgery (10 trials of 530 participants; MD 6.77 mmol/L, 95% CI 3.38 to 10.17). This effect persisted until postoperative day 1 (5 trials of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). Quality of this evidence was moderate. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Outcome data was variably reported at disparate time points and with heterogeneous patient groups. Consequently, the effect size and overall confidence interval was reduced, despite the relatively low inherent risk of bias. There was insufficient evidence on the effect of fluid composition on mortality and organ dysfunction. Confidence intervals of this outcome were wide and the quality of evidence was low (3 trials of 276 participants for mortality; odds ratio (OR) 1.85, 95% CI 0.37 to 9.33; I 2 = 0%). CONCLUSIONS: Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Buffered fluid may have biochemical benefits, including a significant reduction in postoperative hyperchloraemia and metabolic acidosis.

Perioperative buffered versus non-buffered fluid administration for surgery in adults.

BACKGROUND: Perioperative fluid therapy influences clinical outcomes following major surgery. Fluid preparations may be based on a simple non-buffered salt solution, such as normal saline, or may be modified with bicarbonate or bicarbonate precursor buffers, such as maleate, gluconate, lactate or acetate, to better reflect the human physiological state. These latter fluids have theoretical advantages over normal saline in preventing hyperchloraemic acidosis. A number of clinical studies have now compared fluid preparations with and without a buffer to achieve a balanced electrolyte solution for perioperative fluid resuscitation. OBJECTIVES: To review the safety and efficacy of perioperative administration of buffered versus non-buffered fluids for plasma volume expansion or maintenance in adult patients undergoing surgery. SEARCH METHODS: We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4), MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and CINAHL (1982 to May 2011). We handsearched conference abstracts and where possible, contacted leaders in the field. SELECTION CRITERIA: We only included randomized trials of buffered versus non-buffered intravenous fluids for perioperative fluid resuscitation. The trials with other forms of comparisons such as crystalloids versus colloids and colloids versus different colloids were excluded. We also excluded trials using hypertonic fluids and dextrose-based fluids. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the methodological quality of clinical trials. We resolved any disagreements by discussion. We contacted the trial authors to provide additional information where appropriate. We presented pooled estimates of the dichotomous outcomes as odds ratios (OR) and on continuous outcomes as mean differences, with 95% confidence intervals (CI). We analysed data on Review Manager 5.1 using fixed-effect models, and when heterogeneity was high (I² > 40%) random-effect models were used. MAIN RESULTS: We identified 14 publications reporting 13 trials or comparisons with a total of 706 participants. For many of the outcomes reported, there was significant clinical and statistical heterogeneity. The primary outcome of mortality at any time was reported in only three studies with a total of 267 patients. The mortality rate was 2.9% for the buffered fluids group and 1.5% for the non-buffered fluids group but this difference was not statistically significant. The Peto OR was 1.85 (95% CI 0.37 to 9.33, P = 0.45, I(2)= 0%). Organ dysfunction was only presented for renal impairment. There was no difference in renal insufficiency leading to renal replacement therapy between the buffered and non-buffered groups (OR 0.61, 95% CI 0.23 to 1.63, P = 0.32, I(2) = 0%). Markers of organ system failure as assessed by urine output, creatinine and its variables (for renal function), PaC0(2) (respiratory function) and postoperative nausea and vomiting (gastro-intestinal function) showed a statistically significant difference only in PaC0(2) levels. The mean difference was 1.18 with lower PaC0(2) levels in the non-buffered fluid group (95% CI 0.09 to 2.28, P = 0.03, I(2) = 0%) compared to the buffered fluid group.There was no difference in intraoperative blood loss nor the volumes of intraoperative red cell or fresh frozen plasma transfused between groups. There was an increase in platelet transfusion in the non-buffered group which was statistically significant after analysing the transformed data (log transformation because the data were highly skewed).A number of metabolic differences were noted. There was a difference in postoperative pH of 0.06 units, lower in the non-buffered fluid group (95% CI 0.04 to 0.08, P < 0.00001, I(2) = 74%). However, this difference was not maintained on postoperative day one. The non-buffered fluid group also had significantly greater base deficit, serum sodium and chloride levels.There was no difference demonstrated in length of hospital stay and no data were reported on cost or quality of life. AUTHORS' CONCLUSIONS: The administration of buffered fluids to adult patients during surgery is equally safe and effective as the administration of non-buffered saline-based fluids. The use of buffered fluids is associated with less metabolic derangement, in particular hyperchloraemia and metabolic acidosis. Larger studies are needed to assess robust outcomes such as mortality.

Anaesthesia - what has the University of Cape Town contributed?

From humble beginnings, the University of Cape Town's Department of Anaesthesia has played a major role in the development of anaesthesia as a speciality, in South Africa and internationally. We highlight these contributions in clinical service, teaching and research, with particular emphasis on the department's leading role in the evolution of anaesthetic safety in adults and children: from the development of the treatment of malignant hyperthermia, to unique studies in mortality associated with anaesthesia, and modern contributions to improved drug safety. Innovations in anaesthetic techniques have contributed to significant surgical developments, including the first heart transplant. Furthermore, our research has contributed to major advances in obstetric and endocrine anaesthesia, and training in the department is recognised as being among the best in the world.

Place of the colloids in fluid resuscitation of the traumatized patient.

PURPOSE OF REVIEW: The examination of the recent literature aimed at analysing the most recent data that could affect decisions regarding the use of colloids in trauma resuscitation. RECENT FINDINGS: Animal data have generally shown a beneficial effect of colloids in trauma resuscitation, with improvements in capillary leak demonstrated in lung, intestine and brain. In most studies, hydroxyethyl starch resuscitation was more effective than crystalloid and decreased markers of inflammatory processes were observed. Brain injury in animals was attenuated with colloids. In uncontrolled haemorrhage, resuscitation with colloid increased bleeding and mortality.Human studies have also failed to confirm the suggestion that albumin resuscitation may be associated with a worse outcome in head injury. However, there is a strong suggestion that aggressive prehospital resuscitation, particularly with colloid, may be harmful. Studies in burns have consistently shown an improvement in the tendency to fluid overload with the inclusion of colloid in the resuscitation strategy, but so far no outcome benefit has been shown.Two studies of general trauma resuscitation have shown apparent benefit from the use of HES in early resuscitation with reductions in mortality and in renal injury. SUMMARY: Recent trauma studies provide ongoing, but not conclusive, evidence of a benefit from colloid resuscitation in trauma.

Obstetric anaesthesia in low-resource settings.

Close co-operation between obstetricians and obstetric anaesthesia providers is crucial for the safety and comfort of parturients, particularly in low-resource environments. Maternal and foetal mortality is unacceptably high, and the practice of obstetric anaesthesia has an important influence on outcome. Well-conducted national audits have identified the contributing factors to anaesthesia-related deaths. Spinal anaesthesia for caesarean section is the method of choice in the absence of contraindications, but is associated with significant morbidity and mortality. Minimum requirements for safe practice are adequate skills, anaesthesia monitors, disposables and drugs and relevant management protocols for each level of care. The importance of current outreach initiatives is emphasised, and educational resources and the available financial sources discussed. The difficulties of efficient procurement of equipment and drugs are outlined. Guiding principles for the practice of analgesia for labour, anaesthesia for caesarean section and the management of obstetric emergencies, where the anaesthetist also has a central role, are suggested.

Colloids and crystalloids: does it matter to the kidney?

PURPOSE OF REVIEW: To highlight some of the recent key issues surrounding crystalloid and colloid fluid management of critically ill patients. RECENT FINDINGS: Significant developments have been made in the understanding of ionic balance of fluids and their effects on acid-base, the role of hydration and overhydration, alkalinization of fluids in patients at high risk for contrast induced nephropathy, and finally the role of colloids in acute kidney injury. SUMMARY: Despite hydration remaining a key principle in fluid management in many patients, volume overload is of considerable concern. Recent evidence also suggests that balanced electrolyte formulations are preferable to saline-based formulations in a variety of clinical settings. Furthermore, alkalinization of fluids is protective in the setting of contrast-induced nephropathy. Oncotic load appears to be the most important factor in acute kidney injury associated with colloid fluid therapy.

Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery.

BACKGROUND: Hemodynamic responses to vasopressors used during spinal anesthesia for elective Cesarean delivery, have not been well described. This study compared the effects of bolus phenylephrine and ephedrine on maternal cardiac output (CO). The hypothesis was that phenylephrine, but not ephedrine, decreases CO when administered in response to hypotension during spinal anesthesia. METHODS: Forty-three patients were randomized to receive 80 microg of phenylephrine or 10 mg of ephedrine. Both pulse wave form analysis and transthoracic bioimpedance changes were used to estimate stroke volume in each patient. Hemodynamic responses to spinal anesthesia and oxytocin were also recorded. A subgroup of 20 patients was randomized to receive oxytocin compared with oxytocin plus 80 microg of phenylephrine after delivery. RESULTS: Mean CO and maximum absolute response in CO were significantly lower during the 150 s after phenylephrine administration than after ephedrine (6.2 vs. 8.1 l/min, P = 0.001, and 5.2 vs. 9.0 l/min, P < 0.0001, respectively for pulse wave form analysis, and 5.2 vs. 6.3 l/min, P = 0.01 and 4.5 vs. 6.7 l/min, P = 0.0001, respectively for bioimpedance changes). CO changes correlated with heart rate changes. Coadministration of phenylephrine obtunded oxytocin-induced decreases in systemic vascular resistance and increases in heart rate and CO. Trends in CO change were similar using either monitor. CONCLUSIONS: Bolus phenylephrine reduced maternal CO, and decreased CO when compared with ephedrine during elective spinal anesthesia for Cesarean delivery. CO changes correlated with heart rate changes after vasopressor administration, emphasizing the importance of heart rate as a surrogate indicator of CO. Coadministered phenylephrine obtunded hemodynamic responses to oxytocin.

Hydroxyethyl starches: different products--different effects.

With the development of a new generation of hydroxyethyl starches (HES), there has been renewed interest in their clinical potential. High doses of first- and second-generation HES were associated with adverse effects on renal function, coagulation, and tissue storage, thereby limiting their clinical applicability. Newer HES products have lower molar substitution and in vivo molecular weight, resulting in more rapid metabolism and clearance. In this review article, the differences between HES generations are highlighted, with particular emphasis on the improved safety profile of the third generation products. These improvements have been achieved with no loss of efficacy, and they contradict the assumption that efficacy of HES solutions is directly linked to plasma concentration. The impact of source material on structure and pharmacokinetics is highlighted, and the role of the carrier solution is critically assessed.

Longitudinal regional brain volume changes quantified in normal aging and Alzheimer's APP x PS1 mice using MRI.

In humans, mutations of amyloid precursor protein (APP) and presenilins (PS) 1 and 2 are associated with amyloid deposition, brain structural change and cognitive decline, like in Alzheimer's disease (AD). Mice expressing these proteins have illuminated neurodegenerative disease processes but, unlike in humans, quantitative imaging has been little used to systematically determine their effects, or those of normal aging, on brain structure in vivo. Accordingly, we investigated wildtype (WT) and TASTPM mice (expressing human APP(695(K595N, M596L)) x PS1(M146V)) longitudinally using MRI. Automated global and local image registration, allied to a standard digital atlas, provided pairwise segmentation of 13 brain regions. We found the mature mouse brain, unlike in humans, enlarges significantly from 6-14 months old (WT 3.8+/-1.7%, mean+/-SD, P<0.0001). Significant changes were also seen in other WT brain regions, providing an anatomical benchmark for comparing other mouse strains and models of brain disorder. In TASTPM, progressive amyloidosis and astrogliosis, detected immunohistochemically, reflected even larger whole brain changes (5.1+/-1.4%, P<0.0001, transgenexage interaction P=0.0311). Normalising regional volumes to whole brain measurements revealed significant, prolonged, WT-TASTPM volume differences, suggesting transgene effects establish at <6 months old of age in most regions. As in humans, gray matter-rich regions decline with age (e.g. thalamus, cerebral cortex and caudoputamen); ventricles and white matter (corpus callosum, corticospinal tract, fornix system) increase; in TASTPMs such trends often varied significantly from WT (especially hippocampus). The pervasive, age-related structural changes between WT and AD transgenic mice (and mouse and human) suggest subtle but fundamental species differences and AD transgene effects.

Analysis of serial magnetic resonance images of mouse brains using image registration.

The aim of this paper is to investigate techniques that can identify and quantify cross-sectional differences and longitudinal changes in vivo from magnetic resonance images of murine models of brain disease. Two different approaches have been compared. The first approach is a segmentation-based approach: Each subject at each time point is automatically segmented into a number of anatomical structures using atlas-based segmentation. This allows cross-sectional and longitudinal analyses of group differences on a structure-by-structure basis. The second approach is a deformation-based approach: Longitudinal changes are quantified by the registration of each subject's follow-up images to that subject's baseline image. In addition the baseline images can be registered to an atlas allowing voxel-wise analysis of cross-sectional differences between groups. Both approaches have been tested on two groups of mice: A transgenic model of Alzheimer's disease and a wild-type background strain, using serial imaging performed over the age range from 6-14 months. We show that both approaches are able to identify longitudinal and cross-sectional differences. However, atlas-based segmentation suffers from the inability to detect differences across populations and across time in regions which are much smaller than the anatomical regions. In contrast to this, the deformation-based approach can detect statistically significant differences in highly localized areas.

Progression and variability of TNBS colitis-associated inflammation in rats assessed by contrast-enhanced and T2-weighted MRI.

BACKGROUND: A common feature of preclinical models of colitis is that the time-course, magnitude, and persistence of inflammation vary considerably within the experimental animal group. Accordingly, noninvasive, serial quantification of colonic inflammation could advantageously guide dosing regimens and assess drug efficacy, thus enhancing the value of colitis models in research. This investigation using magnetic resonance imaging (MRI) was therefore undertaken to objectively determine inflammatory progression, variability, and response to therapy associated with trinitrobenzene sulfonic acid (TNBS)-induced colitis in Wistar rats. METHODS: Rats underwent TNBS treatment on Day 0 and received sulfasalazine or vehicle (methylcellulose) orally, daily, from Day -1 (prophylactically) or Day 2 (therapeutically). T2-weighted and semidynamic T1-weighted contrast-enhanced MRI (CE-MRI) was repeated over 7-10 days to measure colon wall thickness and perfusion-related aspects of inflammation. Rectal bleeding, stool consistency, and disease activity were scored throughout and colon pathology determined terminally. RESULTS: Principal component analysis of the CE-MRI time-series highlighted colon wall and mesenteric inflammation, which increased by 6-8x naïve values. Peristaltic artifacts were distinguished from perfusion changes using the normalized temporal standard deviation. MRI correlated strongly with terminal colon weight (mean correlation r = 0.8), well with body weight change (r = -0.7), but little with conventional clinical scores. Sulfasalazine reduced inflammation administered prophylactically and therapeutically. CONCLUSIONS: Inflammation and therapeutic efficacy can be sensitively quantified noninvasively using MRI in TNBS-treated rats. This methodology provides unique and objective in vivo measures of inflammation that can guide dosing strategies, enhancing colitis research effectiveness and the assessment of potential IBD therapeutics.

The role of tetrastarches for volume replacement in the perioperative setting.

PURPOSE OF REVIEW: Current opinion in perioperative fluid therapy suggests that the use of colloids to achieve haemodynamic optimization may result in improved clinical outcomes. This has focused interest on the colloid solutions, particularly on the newest of these, the tetrastarches. This review will address the advantages and disadvantages of the starch solutions with particular emphasis on the advantages offered by the tetrastarches, as these products, which have been widely used in Europe for a number of years, have recently been released in the United States. RECENT FINDINGS: The tetrastarches have a molar substitution of 0.4, compared with the older hetastarches that had a molar substitution of 0.7. This results in a lower in-vivo molecular weight leading to more rapid clearance of the starch particles and a reduced incidence of adverse effects such as coagulation disorders and skin itching. It is probable that the more rapidly degradable tetrastarch also decreases, or possibly eliminates, the risk of renal dysfunction that has been associated with some of the earlier starch products. SUMMARY: Tetrastarch represents a substantial advance in colloid therapy, offering good volume effectiveness with a very low risk of adverse effects.