Mortality and the nature of metabolic acidosis in children with shock

HYPOTHESIS: Mortality in children with shock is more closely related to the nature, rather than the magnitude (base deficit/excess), of a metabolic acidosis. OBJECTIVE: To examine the relationship between base excess (BE), hyperlactataemia, hyperchloraemia, 'unmeasured' strong anions, and mortality. DESIGN: Prospective observational study set in a multi-disciplinary Paediatric Intensive Care Unit (PICU). PATIENTS: Forty-six children, median age 6 months (1.5-14.4), median weight 5 kg (3.2-8.8), admitted to PICU with shock. INTERVENTIONS: Predicted mortality was calculated from the paediatric index of mortality (PIM) score. The pH, base excess, serum lactate, corrected chloride, and 'unmeasured' strong anions (Strong Ion Gap) were measured or calculated at admission and 24 h. MEASUREMENTS AND RESULTS: Observed mortality ( n=16) was 35%, with a standardised mortality ratio (SMR) of 1.03 (95% CI 0.71-1.35). There was no significant difference in admission pH or BE between survivors and nonsurvivors. There was no association between elevation of 'unmeasured' anions and mortality, although there was a trend towards hyperchloraemia in survivors ( P=0.08). Admission lactate was higher in nonsurvivors (median 11.6 vs 3.3 mmol/l; P=0.0003). Area under the mortality receiver operating characteristic curve for lactate was 0.83 (955 CI 0.70-0.95), compared to 0.71 (95% CI 0.53-0.88) for the PIM score. Admission lactate level >5 mmol/l had maximum diagnostic efficiency for mortality, with a likelihood ratio of 2.0. CONCLUSION: There is no association between the magnitude of metabolic acidosis, quantified by the base excess, and mortality in children with shock. Hyperlactataemia, but not elevation of 'unmeasured' anions, is predictive of a poor outcome.     

Continuous paravertebral block for pain relief in unilateral multiple rib fracture: A case series

Rib fracture secondary to blunt chest trauma is an indicator of the severity of injury. It is one of the factors associated with morbidity and mortality in blunt chest trauma. Current management of such patients stresses on provision of adequate analgesia and early institution of aggressive physiotherapy. The current study evaluates the analgesic efficacy of continuous thoracic paravertebral infusion of Bupivacaine in unilateral multiple rib fracture (MRF).

Study design

Retrospective, non-randomized case series of 11 patients with unilateral MRF.

Method

Thoracic paravertebral (TPV) space on the side of fractured ribs was catheterized with an epidural catheter. TPV block was initiated with 0.3 ml/kg body weight of 0.25% Bupivacaine with adrenaline. The block was maintained with a continuous infusion of 0.2% Bupivacaine 30 min later, at 0.1–0.2 ml/(kg/h) for a total of 4 days or for the length of admission, which ever was earlier.

Patients were monitored for pain scores at rest and when asked to cough and vital capacity manoeuvre, respiratory rate, oxygen saturation, oxygen index (PaO₂/FiO₂) and percentage change in incentive spirometry.

There were significant improvements in pain scores at rest (p = 0.0097), on cough (p = 0.0039) and vital capacity manoeuvre (p = 0.0078). Other respiratory parameters like respiratory rate, PaO₂ and oxygen index showed persistent improvement from baseline. None of the patients had any complications or side effect related to procedure and technique.

Conclusion

Our study confirms that continuous TPV block is a safe and effective technique for analgesia in patients with unilateral MRF.     

Alcohol and hepatitis C

BACKGROUND/AIMS: Alcohol use and hepatitis C are prominent risk factors for liver injury and this review offers the current understanding of each factor's effects on liver disease. METHODS: A Medline database search was preformed for English articles with a focus on alcohol, hepatitis C and liver disease. Article citations were also considered for further applicable articles, and the strongest studies were included in our review. RESULTS: Up to 60% of patients with hepatitis C have a past history of alcohol use. In patients with hepatitis C, chronic alcohol consumption of more than 5 drinks/day increases the rate of liver fibrosis, risk for cirrhosis, hepatocellular carcinoma, and, possibly, death from liver disease. Numerous studies have further found that even moderate amounts of alcohol can be detrimental to hepatitis C patients. The prevalence of hepatitis C is higher in alcoholics with advanced liver disease than in alcoholics without liver disease. Also, recent alcohol use decreases the response rate to interferon treatment. CONCLUSIONS: Hepatitis C and alcohol use are often co-occurring risk factors for liver disease, and though their interaction is not clear, it is known that heavy drinking significantly promotes liver disease progression.     

C. Hypertension and Systemic Disease

Literature Survey

C. Hypertension and Systemic Disease     

Determinants of third dose of diphtheria–tetanus–pertussis (DTP) completion among children who received DTP1 at rural immunization centres in Pakistan: a cohort study

Objective  In Pakistan, a high proportion of children fail to complete third dose of diphtheria-tetanus-pertussis (DTP3) after having received the first dose (DTP1). A cohort study was conducted to identify the factors predicting three doses of diphtheria–tetanus–pertussis (DTP3) completion among children who have received DTP1 at six centres of Expanded Programme on Immunization (EPI) in rural Pakistan.
Method  We analyzed a cohort of mother–child pairs enrolled at DTP1 between November 2005 and May 2006 in the standard care group of a larger randomized controlled trial. Data were collected from mothers on a structured questionnaire at enrolment, and each child was followed up at clinic visits for 90 days to record dates of DTP2 and DTP3. Multivariable log-binomial regression analysis was performed to identify the independent predictors of DTP3 completion.
Results  Only 39% (149/378) of enrolled children completed DTP3 during the follow-up period. After adjusting for the centre of enrolment in multivariable analysis, DTP3 completion was higher among children who were ≤60 days old at enrolment [adjusted risk ratio (Adj. RR) 1.39, 95% confidence interval (CI): 1.06–1.82], who were living in a household with monthly household income >Rs. 3000 (US$ 50) (Adj. RR 1.76, 95% CI: 1.16–2.65), and who were living ≤10 min away from EPI centre (Adj. RR 1.31, 95% CI: 1.04–1.66).
Conclusions  Interventions targeting childhood immunization dropouts should focus on bringing more children to EPI centres on-time for initial immunization. Relocation of existing EPI centres and creation of new EPI centres at appropriate locations may decrease the travel time to the EPI centres and result in fewer immunization dropouts.     

Characteristics of hepatocellular carcinoma in a murine model of alpha‐1‐antitrypsin deficiency

Aim: Individuals with homozygous (ZZ) alpha‐1‐antitrypsin (α1AT) deficiency are at an increased risk for liver damage, cirrhosis and hepatocellular carcinoma (HCC). The transgenic PiZ mouse, expressing the human α1AT mutant Z gene, is a valuable model for this disease. We studied PiZ mice in order to identify and characterize mechanisms involved in the development of HCC. Methods: Tumor incidence and histology were studied, gene expression levels were surveyed with microarrays, RNA quantified with quantitative real time polymerase chain reaction and protein levels determined with immunoblots and immunohistochemistry. Results: By 16–19 months of age, approximately 69% of the PiZ mice had developed tumors. HCC was present with no evidence of benign adenomas as pre‐cancerous lesions. Tumors showed abnormal mitochondria, variable levels of steatosis, globular inclusions of α1AT mutant Z protein and metastases. PiZ mice that subsequently developed liver tumors had higher serum levels of α1AT mutant Z protein than those that did not develop tumors. Cyclin D1, a cell cycle protein, was upregulated in PiZ livers without tumors compared to Wt. cFOS, a component of AP‐1 that may be involved in transforming cells and MCAM, an adhesion molecule likely involved in tumorigenesis and metastases, were elevated in tumors compared with livers without tumors. Conclusion: In the PiZ model, many of the histological characteristics of HCC recapitulated features seen in human HCC, whether from individuals with homozygous ZZ liver disease or from unrelated causes in individuals that were not homozygous ZZ. The accumulation of mutant Z protein altered the regulation of several genes driving proliferation and tumorigenesis.     

Predictors of myocardial contractile recovery after coronary revascularization in patients with prior myocardial infarction

BackgroundWe sought to explore the prognostic power of certain patient characteristics to predict myocardial contractile recovery after coronary revascularization in patients with prior myocardial infarction.Methods and MaterialsWe enrolled 100 consecutive patients with prior myocardial infarction, significant coronary stenosis/occlusion amenable for revascularization, and regional wall motion abnormality in the distribution of the affected artery. All patients underwent echocardiographic assessment of regional wall motion and left ventricular ejection fraction. Patients underwent coronary revascularization by either percutaneous angioplasty or surgical bypass. Echocardiography was repeated 8 weeks following revascularization. Patients were classified into two groups: Group 1 with evidence of contractile improvement after revascularization at follow-up echocardiography and Group 2 with no such evidence of improvement. The two groups were compared with respect to patients' clinical characteristics and echocardiographic and angiographic data.ResultsPredictors of contractile recovery after revascularization included angina pectoris, the shorter age of infarction at the time of revascularization, a higher baseline left ventricular ejection fraction, a lower baseline wall motion score index, the presence of Grade 2–3 collaterals to the infarct-related artery, and the absence of dyspnea or diabetes mellitus. Stepwise regression analysis identified the presence of Grade 2–3 collaterals to the infarct-related artery and the age of infarction at the time of revascularization as independent predictors of contractile recovery after revascularization.ConclusionsIn patients with prior myocardial infarction, the presence of Grade 2–3 collaterals to the infarct-related artery and the shorter age of infarction at the time of revascularization independently predicted myocardial contractile recovery after coronary revascularization.     

Synthesis and Kinetic Testing of Tetrahydropyrimidine-2-thione and Pyrrole Derivatives as Inhibitors of the Metallo-β-lactamase from Klebsiella pneumonia and Pseudomonas aeruginosa

Metallo‐β‐lactamases (MBLs), produced by an increasing number of bacterial pathogens, facilitate the hydrolysis of many commonly used β‐lactam antibiotics. There are no clinically useful antagonists against MBLs. Two sets of tetrahydropyrimidine‐2‐thione and pyrrole derivatives were synthesized and assayed for their inhibitory effects on the catalytic activity of the IMP‐1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Nine compounds tested ( 1a , 3b , 5c , 6b , 7a , 8a , 11c , 13a , and 16a ) showed micromolar inhibition constants (K_i values range from ～20–80 μm ). Compounds 1c , 2b , and 15a showed only weak inhibition. In silico docking was employed to investigate the binding mode of each enantiomer of the strongest inhibitor, 5c (K_i = 19 ± 9 μm ), as well as 7a (K_i = 21 ± 10 μm ), the strongest inhibitor of the pyrrole series, in the active site of IMP‐1.