Increases in Future AR Count and Size: Overview of the ARTMIP Tier 2 CMIP5/6 Experiment.

The Atmospheric River (AR) Tracking Method Intercomparison Project (ARTMIP) is a community effort to systematically assess how the uncertainties from AR detectors (ARDTs) impact our scientific understanding of ARs. This study describes the ARTMIP Tier 2 experimental design and initial results using the Coupled Model Intercomparison Project (CMIP) Phases 5 and 6 multi-model ensembles. We show that AR statistics from a given ARDT in CMIP5/6 historical simulations compare remarkably well with the MERRA-2 reanalysis. In CMIP5/6 future simulations, most ARDTs project a global increase in AR frequency, counts, and sizes, especially along the western coastlines of the Pacific and Atlantic oceans. We find that the choice of ARDT is the dominant contributor to the uncertainty in projected AR frequency when compared with model choice. These results imply that new projects investigating future changes in ARs should explicitly consider ARDT uncertainty as a core part of the experimental design.

Peri-operative management of the obese surgical patient 2015: Association of Anaesthetists of Great Britain and Ireland Society for Obesity and Bariatric Anaesthesia.

Guidelines are presented for the organisational and clinical peri-operative management of anaesthesia and surgery for patients who are obese, along with a summary of the problems that obesity may cause peri-operatively. The advice presented is based on previously published advice, clinical studies and expert opinion.

Use of microalbuminuria as a predictor of outcome in critically ill patients.

We have investigated the use of microalbuminuria as a predictor of outcome in a pilot study involving 50 critically ill patients in a six-bed hospital intensive care unit (ICU). Urinary microalbumin:creatinine (M:Cr) ratios measured only 6 h after admission to the ICU demonstrated a significant difference (P = 0.01) between survivors and non-survivors, allowing rapid identification of patients at increased risk of developing organ failure and at greater risk of death. This work suggests that earlier identification of these patients using a rapid, simple, inexpensive biochemical test is possible; if confirmed in a larger study, it may be that clinical interventions can be targeted at those most likely to benefit.

Measures of total free radical activity in critically ill patients.

OBJECTIVES: To examine the role played by free radicals during the initial phase of critical illness in patients on an Intensive Care Unit (ICU). DESIGN AND METHODS: Serum total antioxidant status (TAS) and uric acid (UA) levels were measured in 50 patients over 18 hours to represent the initial stage of critical illness. Clinical scoring systems (APACHE II and multiple organ dysfunction scores) were used to assess the degree of organ dysfunction. Outcome was assessed according to patient survival (survivors, n = 36; non-survivors, n = 14). RESULTS: Serum TAS was higher in non-survivors; a similar finding was demonstrated for serum UA. Levels of both biochemical markers were associated with the degree of organ function and with higher antioxidant and UA levels present in patients with more severe organ dysfunction. In addition, serum UA was significantly correlated to serum TAS and probably accounted for much of the antioxidant activity observed. CONCLUSIONS: The increased TAS and UA levels observed may simply be a response to the degree of renal dysfunction observed as those patients with worse renal function had higher TAS and UA levels. In conclusion, measurement of serum TAS appears to be a reflection of UA concentration and results should be interpreted with caution particularly in patients who have renal dysfunction.

N-Acetylcysteine treatment to prevent the progression of multisystem organ failure: a prospective, randomized, placebo-controlled study.

OBJECTIVES: To investigate whether prolonged infusion of N-acetylcysteine (NAC) that is commenced immediately after admission to the intensive care unit could ameliorate the development or progression of multisystem organ failure and improve mortality. DESIGN: Prospective, randomized, double-blinded clinical trial. SETTING: Six-bed intensive care unit in a teaching hospital. PATIENTS: Of the 100 patients recruited (14 withdrew), 86 patients were studied. INTERVENTIONS: After randomization, the treatment group (n = 41) received NAC (150 mg/kg bolus followed by a continuous infusion of 12 mg/kg/hr) and the placebo group (n = 45) received 5% dextrose, from a minimum of 3 days up to a maximum of 5 days. MEASUREMENTS AND MAIN RESULTS: There was no statistically significant difference between the two groups regarding outcome as indicated by mortality and the required days of inotropic support, mechanical ventilation, and intensive care. The time interval between hospital and intensive care unit admission showed great variability, with a median of 24 hrs for the whole sample. By splitting the groups with this median value, the effect of NAC was examined on patients admitted within 24 hrs and after 24 hrs of arrival to the hospital. There was a nonsignificant difference in mortality in favor of NAC. Patients admitted after 24 hrs of hospital admission had a significantly worse mortality in the NAC-treated group (61% vs. 32% for controls; p = .05). CONCLUSIONS: We found a nonsignificant difference in outcome between NAC and placebo-treated patients. Our results suggest that the initiation of NAC treatment >24 hrs after hospital admission may potentially be harmful, and further studies should be undertaken to investigate the clinical use of the early application of NAC in critically ill patients.

The effect of N-acetylcysteine on total serum anti-oxidant potential and urinary albumin excretion in critically ill patients.

OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) when given as an early treatment to critically ill patients on the serum total anti-oxidant potential (TAP) and urine micro-albumin:creatinine (M:Cr) ratio. DESIGN: Prospective, placebo controlled double blinded clinical trial. SETTING: General intensive care unit in a teaching hospital. PATIENTS: Sixty critically ill patients were recruited but ten were withdrawn due to less than 48 h of ICU stay. INTERVENTIONS: After envelope randomisation, patients received either NAC (n = 23): a bolus of 150 mg/kg in 250 ml of 5% dextrose followed by a continuous infusion of 12 mg/kg per h in 500 ml of 5% dextrose over 24 h or, as controls (n = 27), the equal volume of placebo. Treatment lasted for a minimum of 3, up to a maximum of 5, days. Blood and urine samples were collected on admission (0 h) and then 6 hourly up 18 h. MEASUREMENTS AND RESULTS: There was no significant difference between NAC and placebo groups regarding the required length of inotropic support, mechanical ventilation and ICU stay. There was no significant difference in TAP or M:Cr ratio over 18 h or between the groups. CONCLUSIONS: Our results suggest that NAC had no significant effects on the progress of the TAP and the urinary albumin excretion in our patients, which may suggest that NAC at the given dose has no clinical relevance as an early treatment in the critically ill.

Automated analytical systems for drug development studies. V. A system for enzyme kinetic studies.

Two similar automated analytical systems using liquid chromatography (LC) and microdialysis as an on-line sampling technique were applied to studies of enzyme kinetics. 2',3',5'-Triacetyl-6-azauridine (azaribine) with porcine liver esterase (PLE) and N-acetylphenylalanyl-3,5-diiodotyrosine (AcFY') with pepsin were used as model compounds. The microdialysis sampling technique permitted the rapid separation of low molecular weight analytes from macromolecules, thus simultaneously achieving clean-up of the samples and quenching of the reaction. The combination of rapid LC analysis and microdialysis sampling provided selectivity and automation. The systems are rugged and give reproducible results in agreement with those from manual sampling methods.

Cesarean section: medical benefits and costs.

Cesarean section rates have risen dramatically in the U.S. over the past 20 years. Although infant mortality has declined during the same period, there is little evidence that more frequent cesarean surgery is the cause. Cesareans save lives or benefit health in certain circumstances, but the incidence of those indications has not increased. Cesarean section also has risks, the most significant for the infant being iatrogenic prematurity or respiratory disease. Maternal mortality is 2-4 times higher and morbidity is 5-10 times higher after a cesarean compared to vaginal birth. The four indications responsible for most of the rise in cesarean rates--previous cesarean, dystocia, breech presentation, and fetal distress--are those conferring the least clear-cut benefit. Demographically, women who are most likely to experience pregnancy complications, low birth weight births, or infant mortality are least likely to have a cesarean. Social, economic, and other factors seem to have a greater influence on the decision to perform a cesarean than does expected medical benefit. The development of neonatal intensive care, expanded access to prenatal care, and greater availability of abortion and family planning have contributed more to falling infant mortality. It has been estimated that approximately half the cesareans currently performed in the U.S. are medically unnecessary, resulting in considerable avoidable maternal mortality and morbidity, and a cost of over $1 billion each year.

The effect of cardiopulmonary bypass on cholinesterase activity.

Cholinesterase activity was determined in 18 patients who had undergone either hypothermic (n = 9) or normothermic (n = 9) cardiopulmonary bypass. The anaesthetic technique was standardised to avoid agents known to affect cholinesterase. Activity was determined in blood samples taken before the induction of anaesthesia, during cardiopulmonary bypass and for at least 7 days postoperatively. In six patients cholinesterase activity was also measured at 6 weeks postoperatively. All the patients were of normal cholinesterase genotype. In both groups cholinesterase activity fell by approximately 60% coinciding with the start of cardiopulmonary bypass, from a mean of 5976 to 2636 IU.l-1 in the hypothermic group, and from 5901 to 2615 IU.l-1 in the normothermic group (p < 0.001 in both instances) (normal range 4300-10,500 IU.l-1). Cholinesterase activity remained at this reduced level for at least 7 days postoperatively. By 6 weeks, activity had returned to within 7% of pre-induction values. There were no differences in cholinesterase activity between the hypothermic and normothermic groups at any of the sampling times.

Haemodynamic effects and comparison of enoximone, dobutamine and dopamine following mitral valve surgery.

Mitral valve surgery may be complicated by a post-operative low output state requiring inotropic support, and a wide variety of factors may influence the choice of agents used to treat this condition. The authors have examined and compared the haemodynamic effects of the highly specific phosphodiesterase inhibitor enoximone, and the adrenergic agents dobutamine and dopamine in patients undergoing mitral valve surgery. Enoximone, 0.5 mg kg-1 bolus, followed by a continuous infusion of 5 micrograms kg-1 min-1, was compared against dobutamine, 7 micrograms kg-1 min-1, and dopamine, 5 micrograms kg-1 min-1, with the protocol allowing for an increase in the infusion rate by a factor of two if clinical and haemodynamic measurements indicated. All 25 patients receiving enoximone were successfully weaned from cardiopulmonary bypass at the first attempt, with significant increases in cardiac index and stroke index, combined with little or no change in heart rate or pulmonary artery pressures and a highly significant reduction in systemic vascular resistance, and a reduction in mean arterial pressure. Three of the 25 patients receiving dobutamine were withdrawn from the study because of inadequate haemodynamic response, while the remaining 22 patients demonstrated significant increases in heart rate, cardiac index and stroke index, with a reduction in systemic vascular resistance. Nine of the 25 patients receiving dopamine failed to respond adequately, while the remaining 16 demonstrated an increase in heart rate and cardiac index but with little change in stroke index and a modest reduction in systemic vascular resistance. Enoximone has been shown to be a highly effective first-line inotrope in patients following mitral valve surgery with significant advantages over dobutamine and dopamine.

Variation in the depth of the epidural space in successive pregnancies.

The epidural records of 151 patients who had received two effective lumbar epidurals during subsequent labours were studied. For each patient the depth of the epidural space from the skin was recorded at both insertions and the differences between the two measurements compared. Factors which are known to cause a variation in this value were excluded. The skin to epidural space depth was virtually unchanged in 72 (47.7%) of the repeat epidurals. In 18 cases (11.9%) however, the measured depth of the epidural space differed by more than 1.5 cm from one insertion to the next. Possible explanations for these differences are discussed.

Clearance of atracurium and laudanosine in the urine and by continuous venovenous haemofiltration.

We have measured the steady state urinary clearances of atracurium, given by constant infusion, and laudanosine in eight patients undergoing artificial ventilation; all had normal renal function (mean creatinine clearance 81 ml min-1). Mean (SD) urinary clearance of atracurium was 0.55 (0.5) ml kg-1 min-1; that of laudanosine was 0.33 (0.2) ml kg-1 min-1. Simultaneous plasma clearances were 7.1 (1.4) ml kg-1 min-1 and 3.8 (1.5) ml kg-1 min-1, respectively. Notional haemofiltration clearances of the two substances were measured also in seven critically ill patients with renal and respiratory failure undergoing continuous venovenous haemofiltration. Mean (SD) clearances of atracurium and laudanosine in the haemofiltrate fluid were 0.11 (0.06) ml kg-1 min-1 and 0.09 (0.02) ml kg-1 min-1, respectively whilst plasma clearances were atracurium 6.7 (1.8) ml kg-1 min-1 and laudanosine 4.5 (1.8) ml kg-1 min-1. There were no significant differences between the plasma clearances of the drugs in the two groups, despite the difference in severity of sickness. Urinary clearance rates of atracurium and laudanosine were approximately 8 and 9% of that in the plasma, but the haemofiltration clearance of both substances was only 2%.

An assessment of the Cerebrotrac 2500 for continuous monitoring of cerebral function in the intensive care unit.

Experience of the use of the Cerebrotrac 2500 EEG monitor in 17 patients subjected to artificial ventilation in an intensive care unit is reported; seven were receiving continuous sedation with morphine, midazolam and propofol singly or in combination and 10 received both sedation and the neuromuscular blocking agent, atracurium. The processed EEG patterns could not be precisely correlated with a standard clinical scoring system but were useful in determining the adequacy of sedation, particularly when a muscle relaxant was used. The monitor also shows considerable promise in the management of the paralysed patient with widespread convulsive activity in whom ischaemic brain damage may be occurring from epileptiform activity in the absence of any clinical manifestation. The ability to detect cerebral irritability or isolated epileptiform discharges using this apparatus is, however, questionable. The equipment was easy to use and robust; the running costs were 9.5p per hour.