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Fulltext Norepinephrine in Septic Shock: A Systematic Review and Meta-analysis

Ruslan MA, Baharuddin KA, Noor NM, Yazid MB, Noh AYM, Rahman A

West J Emerg Med, 2021 Feb 16;22(2):196-203.
PMID: 33856300 DOI: 10.5811/westjem.2020.10.47825

INTRODUCTION: Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients with septic shock.
METHODS: We searched the Cochrane Central Register of Controlled Trials and Epistemonikos, as well as MEDLINE from 1966 till August 2019. Screening of full texts, evaluation for eligibility, and data extraction were done by four independent reviewers. We estimated risk ratios (RR) and mean differences (MD) using a random-effects model with 95% confidence intervals (CI). The primary outcomes included the number of participants who achieved the target mean arterial pressure (MAP), time to achieve the target MAP, and number of participants with all-cause 28-day mortality. The secondary outcomes included the length of stay in the intensive care unit, length of hospital stay, incidence of arrhythmia and myocardial infarction, vasopressor-free days, and number of participants with all-cause 90-day mortality.
RESULTS: We identified 11 randomized controlled trials with a total of 4,803 participants. There was no difference in the number of participants who achieved the target MAP between those patients receiving norepinephrine and other vasopressors (RR 1.44; 95% CI, 0.32 to 6.54; P = 0.640; I2 = 94%; two trials, 116 participants). There was no significant difference in time to achieve the target MAP (MD -0.05; 95%, CI, -0.32 to 0.21; P = 0.690; I2 = 26%; two trials, 1763 participants) and all-cause 28-day mortality (RR 0.95; 95% CI, 0.89 to 1.02; P = 0.160; I2 = 0%; seven trials, 4,139 participants). Regarding the secondary outcome, norepinephrine may significantly reduce the incidence of arrhythmia as compared to other vasopressors (RR 0.64; 95% CI, 0.42 to 0.97; P = 0.030; I2 = 64%; six trials, 3974 participants). There was no difference in the incidence of myocardial infarction (RR 1.28; 95% CI, 0.79 to 2.09), vasopressor-free day (RR 0.46; 95% CI, -1.82 to 2.74) and all-cause 90-day mortality (RR 1.08; 95% CI, 0.96 to 1.21) between norepinephrine and vasopressors.
CONCLUSION: In minimizing the occurrence of an arrhythmia, norepinephrine is superior to other vasopressors, making it safe to be used in septic shock. However, there was insufficient evidence concerning mortality and achievement of the target MAP outcomes.

Matched MeSH terms: Shock, Septic/mortality
Sepsis, severe sepsis and septic shock in paediatric multiple organ dysfunction syndrome

Goh A, Lum L

J Paediatr Child Health, 1999 Oct;35(5):488-92.
PMID: 10571765

OBJECTIVES: To determine the association between severity of sepsis with outcome and severity of illness in children with multiple organ dysfunction syndrome (MODS).
MATERIALS: Four hundred and ninety-five consecutive paediatric intensive care unit (PICU) admissions were analysed. multiple organ dysfunction syndrome was defined as simultaneous dysfunction of >/= 2 organ system and sepsis by the American College of Chest Physicians and Society of Critical Care Medicine Consensus Conference definition.
RESULTS: Eighty-four patients developed MODS. The incidence of sepsis, severe sepsis and septic shock in these patients was 10.7%, 23.8% and 17.9%, respectively. Worsening categories of sepsis were associated with: (1) a higher mean admission Paediatric Risk of Mortality (PRISM II): 36.6 +/- 25.9, 56.8 +/- 32.1 and 73.6 +/- 28.5%, respectively (P = 0. 005), (2) a larger number of organ dysfunctions: mean MODS index of 37%, 46% and 58%, respectively (P = 0.007), and (3) a higher mortality: 22.2%, 65% and 80%, respectively (P = 0.03).
CONCLUSION: Presence of sepsis, severe sepsis and septic shock was associated with an increasing severity of illness, increased number of organ dysfunctions and a distinct risk of mortality among critically ill children.

Matched MeSH terms: Shock, Septic/mortality
Pediatric melioidosis in Pahang, Malaysia

How HS, Ng KH, Yeo HB, Tee HP, Shah A

J Microbiol Immunol Infect, 2005 Oct;38(5):314-9.
PMID: 16211138

Melioidosis is much less common in children than in adults. This study investigated the incidence, demographic characteristics, presenting symptoms and outcome of pediatric melioidosis in Pahang, Malaysia. This retrospective study included patients < or =18 years old with positive body fluid cultures for Burkholderia pseudomallei from January 2000 to June 2003. Data on culture results were obtained from 2 referral hospitals. The incidence of pediatric melioidosis was 0.68/100,000 population per year. Of the 13 patients identified during the study period, 10 were male; 9 were Malays, 2 were Indians and 2 were aborigines. The mean age of these patients was 9.5 +/- 5.4 years. None of the patients had a previous history of confirmed melioidosis or predisposing factors for infection. Localized melioidosis was the most common presentation (46.2%) followed by melioidosis with septic shock (38.4%). Among patients with localized melioidosis, head and neck involvement (83.3%) was the most common presentation (2 patients with cervical abscesses, 1 with submandibular abscesses and 2 with acute suppurative parotitis) and another patient had right axillary abscess. All of the patients with septic shock had pneumonia and 2 of them had multi-organ involvement. The mortality among patients with septic shock was 80% and death occurred within 24 h of admission in all cases. In contrast, no complications or death occurred among patients with localized melioidosis. Melioidosis with septic shock is less common than localized melioidosis in pediatric patients, but is associated with very high mortality.

Matched MeSH terms: Shock, Septic/mortality
Sepsis in tropical regions: Report from the task force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine

McGloughlin S, Richards GA, Nor MBM, Prayag S, Baker T, Amin P

J Crit Care, 2018 08;46:115-118.
PMID: 29310974 DOI: 10.1016/j.jcrc.2017.12.018

Sepsis and septic shock in the tropics are caused by a wide array of organisms. These infections are encountered mainly in low and middle-income countries (LMIC) where a lack of infrastructure and medical facilities contribute to the high morbidity and mortality. Published sepsis guidelines are based on studies primarily performed in high income countries and as such recommendations may or may not be relevant to practice in the tropics. Failure to adhere to guidelines, particularly among non-intensive care specialists even in high-income countries, is an area of concern for sepsis management. Additionally, inappropriate use of antimicrobials has led to significant antimicrobial resistance. Access to rapid, low-cost, and accurate diagnostic tests is critical in countries where tropical diseases are prevalent to facilitate early diagnosis and treatment. Implementation of performance improvement programs may improve outcomes for patients with sepsis and the addition of resuscitation and treatment bundles may further reduce mortality. Associated co-morbidities such as malnutrition and HIV influence outcomes and must be considered.

Matched MeSH terms: Shock, Septic/mortality
Fulltext Global utilization of low-dose corticosteroids in severe sepsis and septic shock: a report from the PROGRESS registry

Beale R, Janes JM, Brunkhorst FM, Dobb G, Levy MM, Martin GS, et al.

Crit Care, 2010;14(3):R102.
PMID: 20525247 DOI: 10.1186/cc9044

INTRODUCTION: The benefits and use of low-dose corticosteroids (LDCs) in severe sepsis and septic shock remain controversial. Surviving sepsis campaign guidelines suggest LDC use for septic shock patients poorly responsive to fluid resuscitation and vasopressor therapy. Their use is suspected to be wide-spread, but paucity of data regarding global practice exists. The purpose of this study was to compare baseline characteristics and clinical outcomes of patients treated or not treated with LDC from the international PROGRESS (PROmoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis.
METHODS: Patients enrolled in the PROGRESS registry were evaluated for use of vasopressor and LDC (equivalent or lesser potency to hydrocortisone 50 mg six-hourly plus 50 microg 9-alpha-fludrocortisone) for treatment of severe sepsis at any time in intensive care units (ICUs). Baseline characteristics and hospital mortality were analyzed, and logistic regression techniques used to develop propensity score and outcome models adjusted for baseline imbalances between groups.
RESULTS: A total of 8,968 patients with severe sepsis and sufficient data for analysis were studied. A total of 79.8% (7,160/8,968) of patients received vasopressors, and 34.0% (3,051/8,968) of patients received LDC. Regional use of LDC was highest in Europe (51.1%) and lowest in Asia (21.6%). Country use was highest in Brazil (62.9%) and lowest in Malaysia (9.0%). A total of 14.2% of patients on LDC were not receiving any vasopressor therapy. LDC patients were older, had more co-morbidities and higher disease severity scores. Patients receiving LDC spent longer in ICU than patients who did not (median of 12 versus 8 days; P <0.001). Overall hospital mortality rates were greater in the LDC than in the non-LDC group (58.0% versus 43.0%; P <0.001). After adjusting for baseline imbalances, in all mortality models (with vasopressor use), a consistent association remained between LDC and hospital mortality (odds ratios varying from 1.30 to 1.47).
CONCLUSIONS: Widespread use of LDC for the treatment of severe sepsis with significant regional and country variation exists. In this study, 14.2% of patients received LDC despite the absence of evidence of shock. Hospital mortality was higher in the LDC group and remained higher after adjustment for key determinates of mortality.

Matched MeSH terms: Shock, Septic/mortality