Bacillus Calmette-Guérin vaccination and clinical characteristics and outcomes of COVID-19 in Rhode Island, United States: a cohort study.

Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic, and there is limited data on effective therapies. Bacillus Calmette-Guérin (BCG) vaccine, a live-attenuated strain derived from an isolate of Mycobacterium bovis and originally designed to prevent tuberculosis, has shown some efficacy against infection with unrelated pathogens. In this study, we reviewed 120 consecutive adult patients (≥18 years old) with COVID-19 at a major federally qualified health centre in Rhode Island, United States from 19 March to 29 April 2020. Median age was 39.5 years (interquartile range, 27.0-50.0), 30% were male and 87.5% were Latino/Hispanics. Eighty-two (68.3%) patients had BCG vaccination. Individuals with BCG vaccination were less likely to require hospital admission during the disease course (3.7% vs. 15.8%, P = 0.019). This association remained unchanged after adjusting for demographics and comorbidities (P = 0.017) using multivariate regression analysis. The finding from our study suggests the potential of BCG in preventing more severe COVID-19.

ECMO in acute and chronic adult respiratory failure: recent trends and future directions.

Extracorporeal membrane oxygenation (ECMO) can be used to preserve or enhance systemic oxygen delivery in patients with refractory cardiac or respiratory failure. Although widely accepted as a standard of care for many indications in children and for adult cardiogenic shock, ECMO for adult respiratory failure is more controversial. This controversy arose over thirty years ago after the disappointing results of the first flawed, randomized study and is fueled by a group of non-ECMO clinicians who repeatedly criticize the methodology of more recent studies which show probable benefit. In spite of this, there is probably now more evidence to support the use of ECMO in refractory acute respiratory distress syndrome than for any other form of rescue therapy. The purpose of this review is to update clinicians regarding trends in ECMO research over the last 12 months and speculate on how the clinical use of ECMO and associated technology will evolve.

Correlation of thromboelastography with standard tests of anticoagulation in paediatric patients receiving extracorporeal life support.

UNLABELLED: Children requiring extracorporeal life support (ECLS) are at significant risk for thrombotic and haemorrhagic complications. Thromboelastography (TEG) is increasingly being used to assist in monitoring the coagulation status of critically ill patients. Its role in heparinised children receiving ECLS is unknown. METHODS: A retrospective review of TEG in 27 children (mean age 2 years and 8 months) receiving ECLS in a tertiary paediatric intensive care unit between December 2006 and April 2008. Paired TEG (kaolin and heparinase) analysis was performed on 171 occasions. On all occasions activated partial thromboplastin time (APTT) and platelet count were performed within 4 hours of the TEG (mean 6.5 minutes after TEG). On 158 occasions, the activated clotting time (ACT) was measured simultaneously with TEG. RESULTS: The TEG (kaolin) sample was not interpretable due to the heparin effect in 89 (52%) samples. There was a weak correlation between TEG (heparinase) variables and APTT, and between TEG and ACT with a stronger correlation between TEG (Maximum amplitude) and platelet count. CONCLUSION: TEG monitoring should always include paired samples in heparinised children on ECLS. In this heterogeneous population, weak, and moderate correlations exist between TEG and standard haematological tests. Prospective studies, with simultaneous sampling for TEG and conventional laboratory tests, must be performed in order to establish its absolute utility as a clinical tool in this population.

IL-6 and IL-8 levels after cardiopulmonary bypass are not affected by surface coating.

UNLABELLED: BACKGROUND.:Contact of blood with the surfaces of the cardiopulmonary bypass (CPB) circuit has been implicated as a cause of the inflammatory response. We undertook a prospective randomized trial of 200 pediatric patients, all with a calculated total bypass flow of less than 2.3 L/min (< 0.96 L/m2/min). METHODS: Patients were randomly assigned to 1 of 4 CPB groups: (1) Nonheparin-bonded circuit with no albumin preprime; (2) Nonheparin-bonded circuit with albumin preprime; (3) Heparin-bonded circuit with no albumin preprime; (4) Heparin-bonded circuit with albumin preprime. Measurements of cytokines, (interleukin [IL]-6, IL-8) and blood cell counts were made prebypass and 6 and 24 hours after institution of cardiopulmonary bypass. RESULTS: Analysis of variance showed no significant difference in any of the clinical or biochemical characteristics of the 4 groups. The interaction between heparin-bonded oxygenators and albumin preprime was not significant. No important differences in IL-6 or IL-8 concentrations were noted after CPB using either heparin or nonheparin-bonded oxygenators with albumin or albumin free preprime using two-way analysis of variance. CONCLUSIONS: Albumin preprime and heparin-bonding do not attenuate the inflammatory response component attributable to the concentration of these markers.

Continuous plasmafiltration in sepsis syndrome. Plasmafiltration in Sepsis Study Group.

OBJECTIVE: To assess the effect of plasmafiltration (PF) on biochemical markers of inflammation, cytokines, organ dysfunction, and 14-day mortality in human sepsis. DESIGN: Multicenter, prospective, randomized, controlled clinical trial. SETTING: Seven university-affiliated intensive care units. PATIENTS: Thirty patients (22 adults, eight children) with new (<24 hrs) clinical evidence of infection and sepsis syndrome were enrolled. Fourteen of 30 (nine adults, five children) were randomized to PF. INTERVENTIONS: All patients received protocol-driven supportive intensive care, and those randomized to PF received continuous plasma exchange for 34 hrs using a hollow-fiber plasma filter. MEASUREMENTS AND MAIN RESULTS: Illness severity and risk of death were calculated with the Pediatric Risk of Mortality (children) and the Acute Physiology and Chronic Health Evaluation II (adults) scales. Plasma samples (0, 6, 24, and 48 hrs) were assayed for acute-phase proteins (albumin, globulin, C-reactive protein, alpha1-antitrypsin, haptoglobin), inflammatory mediators (complement fragment C3, thromboxane B2), and cytokines (interleukin-6, granulocyte colony-stimulating factor, leukemia inhibitory factor). Sieving coefficients were estimated from filtrate concentrations at 3 hrs. The two groups were matched for incidence of septic shock (13 of 14 vs. 11 of 16), refractory shock (three of 14 vs. six of 16), bacteremia (six of 14 vs. five of 16), severity of illness, and calculated risk of death (0.68 vs. 0.64). There was no difference in mortality. Eight of 14 PF patients (57%) and eight of 16 controls (50%) survived for 14 days (p = .73, Fisher's exact test). Multiple logistic regression revealed age (odds ratio, 16.4:1; 95% confidence interval, 2.12-infinity) and shock (10.6:1; 1.32-infinity) as significant predictors of death; plasmafiltration was associated with a nonsignificant reduction in the risk of death (odds ratio, 1.78:1; 95% confidence interval, 0.20-18.1). The mean (SD) number of organs failing in the first 7 days in the PF group was 2.57 (0.94) vs. 2.94 (0.85) in controls (p = .37, Mann-Whitney U test). Both groups had similarly elevated plasma concentrations of all inflammatory mediators except complement fragment C3 at study entry. Leukemia inhibitory factor was detectable in four patients only. PF did not influence mean concentrations of interleukin-6, granulocyte colony-stimulating factor, thromboxane B2, total white cell count, neutrophil count, or platelet count, but it was associated with significant reductions of alpha1-antitrypsin, haptoglobin, C-reactive protein, and complement fragment C3 in the first 6 hrs (p < .05). The sieving coefficients for all inflammatory mediators approached unity. CONCLUSIONS: PF caused a significant attenuation of the acute-phase response in sepsis. There was no significant difference in mortality, but there was a trend toward fewer organs failing in the PF group that suggests that this procedure might be beneficial.

Transferred patients--more complex and more costly?

AN-DRGs have some splits which take illness severity and complexity into account. Age is also often used as a proxy for severity of illness. The need to transfer a patient may be a marker of illness severity or complexity and therefore resource utilisation. This is supported by studies of patients transferred to intensive care units. Data on the costs and outcomes of all transferred patients should be collected; depending on the results, refinements of DRGs may be indicated.

Haemodynamic effects of arteriovenous and venovenous haemofiltration in piglets.

The aim of this study was to compare the early haemodynamic effects of continuous arteriovenous haemofiltration (CAVH) with those of continuous venovenous haemofiltration (CVVH) in normal and endotoxic piglets, within the framework of a two-period cross-over trial. Sixteen domestic piglets (weight 6-18 kg) underwent 1 h of CAVH followed by 1 h of CVVH or 1 h of CVVH followed by 1 h of CAVH. Six were pre-treated with a graded endotoxin infusion to simulate clinical sepsis. The main measurements included: heart rate; mean arterial (MAP), pulmonary artery, central venous and pulmonary artery occlusion pressures; thermodilution cardiac output; and calculated systemic (SVRI) and pulmonary vascular resistance indexes. Each measurement was performed immediately before and 30 min after commencement of each technique of filtration. Commencement of haemofiltration in normal piglets caused minimal haemodynamic effects. In endotoxic piglets, commencement of filtration, whether CAVH or CVVH, caused a haemodynamic change which was significantly more pronounced in the first filter (SVRI -39%, MAP -32%) than the second filter (SVRI +22%, MAP +0.9%) (SVRI, P=0.01, first filter vs. second) (MAP, P=0.009 first filter vs. second). In conclusion, there were no significant differences between the early haemodynamic effects of CAVH and CVVH in normal or endotoxic piglets. The haemodynamic effects of either technique may become more significant in the presence of sepsis.

High frequency oscillation in newborn infants with respiratory failure.

OBJECTIVE: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV). METHODOLOGY: Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation. RESULTS: Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights < 1500 g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight > 1500 g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing < 1500 g who received HFOV in the first week of life developed periventricular haemorrhage. CONCLUSION: The initial results of HFOV for severe failure were encouraging although a learning curve was encountered with its introduction.

Blood filtration in children with severe sepsis: safe adjunctive therapy.

OBJECTIVE: To review the safety and efficacy of haemofiltration and plasmafiltration in children with severe sepsis. DESIGN: Retrospective case notes analysis. SETTING: University Paediatric Intensive Care Unit. PATIENTS: All children admitted to the intensive care unit between November 1985 and May 1992 with a primary diagnosis of severe sepsis who also received blood filtration therapy. INTERVENTIONS: Continuous haemofiltration (HF) 18 patients; continuous haemofiltration and plasmafiltration (PF) 9 patients. MEASUREMENTS AND RESULTS: 27 children with sepsis-induced MOSF, median age 26.6 months (range 0.33-185), median weight 12 kg (range 2.5-58), mean PRISM score 19.4 (SD 8.6), mean number of organs failing 2.78 (SD 0.9) received filtration for a median duration of 36 hours (range 2-145). Eight (30%) survived (HF 5/18, PF 3/9). There was no significant difference in the demographic features between the HF group and the PF group and no difference in mortality. The two groups were pooled to assess the effect of commencement of filtration on clinical wellbeing. Arterial blood gases, electrolytes, full blood examination, ventilator settings and doses of inotropes were recorded immediately prior to commencement of filtration and 18 h after commencement. Serum anion gap and osmolality were calculated using conventional formulae. There were no significant changes in the level of cardiorespiratory support, or biochemical markers of severity following commencement of filtration. Platelet count fell 32% (p = 0.029) but no bleeding was encountered. No severe complications were observed during 1222 h of filtration. No bleeding or infection was observed at the site of cannulation. One child developed haemodynamic instability following commencement of plasmafiltration necessitating abandonment of the procedure. CONCLUSION: Haemofiltration or plasmafiltration can be performed safely in children with severe sepsis but their effect on outcome remains unknown.

Median nerve somatosensory evoked potentials in children receiving ECMO.

Somatosensory evoked potentials (SEPs) were recorded from 11 patients receiving venoarterial extracorporeal membrane oxygenation (ECMO). Cortical responses recorded from the right and left hemispheres were compared to those from 2 other groups of children who were not receiving ECMO. One group consisted of 99 brain-injured patients, while the other consisted of a group of 17 neurologically normal controls. SEP responses from each hemisphere were categorized into 3 grades based on the N20 component--normal latency, abnormal (latency increased > 3 S.D.), or absent. For ECMO patients, 15% of tests disclosed a disagreement between the right and left hemispheres, while 27% of tests from the control group revealed a disagreement between the right and left hemispheres. SEPs were normal over the right hemisphere in 9 patients. Central conduction times obtained from the right and left hemispheres were similar in ECMO patients and were not different from those recorded from a group of patients suffering hypoxic-ischemic injuries and a group of normal controls who did not receive ECMO. The results of this pilot study suggest that SEPs may be employed to evaluate ECMO patients as they are in other brain-injured patients.

A comparison of solute clearance during continuous hemofiltration, hemodiafiltration, and hemodialysis using a polysulfone hemofilter.

The clearance of urea, creatinine, amino acids, vancomycin, and phenytoin was measured in vivo in a small animal model during continuous venovenous (CVV) hemofiltration, CVV hemodiafiltration, and CVV hemodialysis using a 0.25 m2 polysulfone hemofilter. Six domestic piglets (weighing 6-11.8 kg) each received 1 hr of all three techniques in random order. Blood flow was 50 ml/min. During CVV hemofiltration, filtrate production was 500 ml/hr and dialysate flow was zero. During CVV hemodiafiltration, filtrate production was 250 ml/hr and dialysate flow was 250 ml/hr. During CVV hemodialysis, net filtrate production was zero and dialysate flow was 500 ml/hr. The ratio of concentration of solute in filter effluent to concentration in whole plasma was derived for each solute during each of the three techniques. Mean (SD) effluent:plasma ratio for urea during CVV hemofiltration was 0.957 (0.038), CVV hemodiafiltration 0.876 (0.109), and CVV hemodialysis 0.754 (0.123); creatinine 0.942 (0.05), 0.934 (0.056), and 0.814 (0.057); amino acids 0.996 (0.344), 0.904 (0.196), and 0.778 (0.18). For small unbound solutes, there is a decrease in clearance of 6% from CVV hemofiltration to CVV hemodiafiltration and a further decrease of 14% from hemodiafiltration to hemodialysis. The effluent:plasma ratio for vancomycin during CVV hemofiltration was 0.739 (0.082), CVV hemodiafiltration 0.643(0.063), and CVV hemodialysis 0.509 (0.081), corresponding to a decrease of 30% from CVV hemofiltration to CVV hemodialysis. The effluent:plasma ratio for phenytoin was 0.302 (0.028) during CVV hemofiltration and was not significantly different during CVV hemodiafiltration or CVV hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal membrane oxygenation life support: a new approach.

The use of extracorporeal life support (ECLS) is considered in children who (1) have an acute life-threatening heart or lung disease, (2) are normal before the illness and are likely to be normal if they survive, and (3) have an 80% chance of death. Our use of a constrained vortex pump (CVP) offers a number of potential advantages compared to a roller pump. The circuit is designed to provide the capability of changing over to a new circuit while maintaining full support and is primed to match the biochemistry of the patient as closely as possible. Since May 1989 at the Royal Children's Hospital, Melbourne, Australia, we have provided ECLS to 30 neonates (20 of whom survived) and 22 children (eight of whom survived). ECLS is a useful technique for supporting patients who are unable to be adequately ventilated or oxygenated or who have an inadequate cardiac output.

Continuous venovenous hemofiltration in the management of acute decompensation in inborn errors of metabolism.

Continuous venovenous hemofiltration was used to treat two neonates, one with maple syrup urine disease and the other with an inborn error of long-chain fatty acid oxidation. The latter infant had hypoglycemia, hyperammonemia and lactic acidosis. In both cases, acceptable biochemical control was achieved within 8 hours. This therapy offers the potential to overcome acute crises rapidly in a wide range of inborn errors of intermediary metabolism.

Mechanical ventilation of paediatric patients with asthma: short and long term outcome.

In the 7 years from 1982 to 1988, 10,639 children with acute asthma were admitted to the Royal Children's Hospital, Melbourne. Of these, 262 children (2%) were treated in the Intensive Care Unit. Twenty-seven required mechanical ventilation on 34 occasions, being 0.3% of hospital asthma admissions. Five patients died, four due to brain death following respiratory arrest prior to intubation. The main complications were (i) barotrauma, which occurred in five patients on seven occasions (20%); (ii) a reversible myopathy which occurred in three patients treated with high dose corticosteroids and muscle relaxants. Follow-up of patients ventilated in intensive care revealed that all but one of the initial survivors was alive 1-5 years later, all patients required subsequent readmission to hospital for treatment of acute asthma and 78% had persistent rather than episodic asthma. Although uncommon, an episode of ventilation has a major impact on the family's understanding and future management of acute asthma.

Complications resulting from use of arterial catheters: retrograde flow and rapid elevation in blood pressure.

Arterial catheters, routinely used in neonatal intensive care units, have been associated with serious complications. In the present studies, retrograde blood flow occurring during routine flushing of peripheral and umbilical catheters is described. This retrograde flow is associated with a significant elevation of blood pressure at distant sites. These phenomena depend on the volume flushed and on the velocity of the flushing process. These phenomena can be prevented by flushing a small volume of 0.5 mL for a period of five seconds.

Perinatal factors, periventricular haemorrhage and mortality in very low birthweight infants.

In a population of 225 very low birthweight infants born over a 21 month period the cerebroventricular system was scanned by ultrasound. One third of the infants developed a periventricular haemorrhage; in 41% of infants the haemorrhage was detected before an hour of age and 66% of all haemorrhages occurred within the first 24 hours. Statistically significant associations with periventricular haemorrhage included vaginal delivery, endotracheal intubation and intravenous sodium bicarbonate when this was administered in the first 24 hours. In a stepwise regression analysis, however, these and other potentially significant variables added little to the total accountable variance. A similar analysis of perinatal factors and mortality revealed that decreasing gestation was the major association with death.

Survival after prolonged persistent pulmonary hypertension.

We report an infant with prolonged persistent pulmonary hypertension (PPH) who failed to respond to various mechanical and pharmacological therapies but who showed spontaneous improvement at 13 days of age. We therefore stress that assisted ventilation should be continued in PPH without major structural cardiac or pulmonary abnormality or ongoing iatrogenic complications, as recovery may occur at any time.