Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity

Rivers, Emanuel P.; McIntyre, Lauralyn; Morro, David C.; Rivers, Kandis

doi:10.1503/cmaj.050632

Cited by 139 publications

(109 citation statements)

References 167 publications

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“…Patients who arrive at the ICU with a seemingly benign infection can progress within hours to a devastating condition [26,27] . A delay in the diagnosis and management of critically ill patients during the first six hours of ICU admission has been associated with higher mortality rates and increased utilization of hospital resources [28,29] .…”

Section: Discussionmentioning

confidence: 99%

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors

Sun

Zhang

et al. 2012

Acta Pharmacol Sin

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Aim: To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock. Methods: Kunming mice were injected with lipopolysaccharide (LPS 30 mg/kg, ip) to induce endotoxic shock. Anisodamine (12.5, 25, and 50 mg/kg, ip) and neostigmine (12.5, 25, and 50 μg/kg, ip) were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-α and IL-1β were analyzed using ELISA assays. The effects of anisodamine and neostigmine were also examined in α7 nicotinic acetylcholine receptor (α7 nAChR) knockout mice with endotoxic shock and in Beagle dogs with hemorrhagic shock. Results: In mice with experimental endotoxemia, combined administration of anisodamine and neostigmine significantly increased the survival rate and decreased the serum levels of inflammatory cytokines, as compared to those produced by either drug alone. The antishock effect of combined anisodamine and neostigmine was abolished in α7 nAChR knockout mice. On the other hand, intravenous injection of the combined anisodamine and neostigmine, or the selective α7 nAChR agonist PNU282987 exerted similar anti-shock effects in dogs with hemorrhagic shock. Conclusion:The results demonstrate that combined administration of anisodamine and neostigmine produces significant anti-shock effects, which involves activation of α7 nAChRs.

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Section: Discussionmentioning

confidence: 99%

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors

Sun

Zhang

et al. 2012

Acta Pharmacol Sin

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“…Microorganisms do not need to pass into the blood for the development of sepsis. The local or systemic extension of signal products and toxins of the pathogen might initiate sepsis [7]. Multiple bacteria can be responsible in some sepsis patients [8].…”

Section: Incidence and Causesmentioning

confidence: 99%

“…Protection is the most important way of reducing morbidity and mortality rates. Most of the attacks are nosocomial [7].…”

Section: Treatmentmentioning

confidence: 99%

Sepsis and Septic Shock: Current Treatment Strategies and New Approaches

et al. 2017

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Sepsis is a complex condition characterized by the simultaneous activation of inflammation and coagulation in response to microbial insult. These events manifest as systemic inflammatory response syndrome or sepsis symptoms through the release of proinflammatory cytokines, procoagulants, and adhesion molecules from immune cells and/or damaged endothelium. Today, sepsis is a severe multisystem disease with difficult treatments for its manifestations and high mortality rates. In the last two decades in particular, many studies have been conducted on sepsis that cause shock, multiorgan dysfunction, and organ failure by especially leading to hemodynamic changes. In sepsis, increasing antibiotic resistance and medicine-resistant hemodynamic changes have resulted in further research on new treatment modalities in addition to classical treatments. In the last decade, the sepsis physiopathology has been elucidated. Various therapeutic agents have been used in addition to antibiotherapy, but no satisfactory results have been obtained. This review summarizes the sepsis pathophysiology, current treatment protocols, and new approaches.

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“…Implementasi dari (Early Goal Directed Therapy) EGDT pada penelitian awal yang dilakukan oleh Rivers, dkk. 24 tahun 2001, menunjukkan bahwa dapat menurunkan laju mortalitas dari 46,5% menjadi 30,5%. Penelitian lain menunjukkan bahwa pengenalan dan implementasi dini EGDT dalam penanganan sepsis berat serta inisiasi antibiotik dini, dapat menurunakan laju mortalitas dari 51,4% menjadi 27,0%.…”

Section: Diskusiunclassified

Peran Bersihan Laktat pada Kesintasan Pasien Sepsis Berat

Hambali¹,

Chen²,

Widodo³

et al. 2016

JPDI

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ABSTRAKPendahuluan. Sepsis Berat merupakan masalah kesehatan dengan tingkat mortalitas yang tinggi serta insiden yang terus meningkat. Bersihan laktat menggambarkan kinetika metabolisme anaerob pasien sepsis berat dan merupakan parameter yang potensial untuk mengevaluasi kondisi penyakit dan intervensi pengobatan yang didapat pasien. Namun demikian, hubungan antara bersihan laktat terhadap terjadinya kematian pasien sepsis berat belum diketahui. Berdasarkan hal tersebut, penelitian ini dilakukan untuk mengetahui pengaruh bersihan laktat terhadap kesintasan pasien dengan sepsis berat, serta faktor-faktor perancu yang mempengaruhi hubungan tersebut.Metode. Penelitian ini merupakan penelitian kohort prospektif yang dilaksanakan di Unit Gawat Darurat dan ruang perawatan Rumah Sakit dr. Cipto Mangunkusumo (RSCM) pada bulan Maret-Mei 2011. Pasien termasuk dalam kelompok bersihan laktat tinggi bila terdapat perbedaan kadar laktat ≥10% dalam 6 jam pertama pengobatan, sedangkan perbedaan <10% termasuk ke dalam kelompok bersihan laktat rendah. Selanjutnya, dilakukan observasi terhadap terjadinya kematian dalam 10 hari pertama perawatan pada kedua kelompok. Data yang terkumpul selanjutnya dianalisis mengunakan uji statistik log-rank test, serta dicari nilai hazard ratio dengan menggunakan uji cox regression model. Selanjutnya, dilakukan analisis variabel perancu dengan menggunakan uji cox regression.Hasil. Laju kesintasan kelompok bersihan laktat tinggi dan rendah masing-masing sebesar 60,0% dan 26,7% (p=0,004). Median kesintasan yaitu 3 hari pada bersihan laktat rendah, sedangkan kematian tidak mencapai 50% pada bersihan laktat tinggi. Interkuartil I kedua kelompok berturut-turut sebesar 1 dan 4 hari. Dari analisis didapatkan hazard ratio sebesar 2,87 (IK 95%; 1,41-5,83). Pada analisis multivariat keberadaan syok sepsis, skor SOFA, penggunaan vasopresor/inotropik, transfusi dan cairan resusitasi, tidak ada yang mengubah nilai hazard ratio >10%. Oleh karena itu, tidak ada yang memenuhi syarat untuk disebut sebagai perancu.Simpulan. Pasien bersihan laktat tinggi memiliki kesintasan lebih tinggi dibandingkan pasien bersihan laktat rendah dan hubungan tersebut tidak dipengaruhi perancu.

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Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity

Abstract: CMAJ 2005;173(9):1054-65 the cardiovascular insufficiency that accompany this transition may not be detected by vital signs nor SIRS criteria. 18 It is at this critical juncture that outcomes can be much improved.

Cited by 139 publications

References 167 publications

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors

Sepsis and Septic Shock: Current Treatment Strategies and New Approaches

Peran Bersihan Laktat pada Kesintasan Pasien Sepsis Berat

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