In septic shock

More potent than dopamine and may be more effective in managing hypotension in septic shock... 

Not yet a first-line agent (the recent Vasopressin in Septic Shock Trial [VASST] showed no difference in 28-d mortality when vasopressin was compared with norepinephrine)... 

Discontinue infusion when the arterial pH reaches 7.5 D Do not administer in patients in septic shock... 

The fluid and protein shift into the abdomen (called third-spacing) may be so dramatic that circulating blood volume is decreased, which causes decreased cardiac output and hypovolemic shock. Accompanying fever, vomiting, or diarrhea may worsen the fluid imbalance. A reflex sympathetic response, manifested by sweating, tachycardia, and vasoconstriction, may be evident. With an inflamed peritoneum, bacteria and endotoxins are absorbed easily into the bloodstream (translocation), and this may result in septic shock. Other foreign substances present in the peritoneal cavity potentiate peritonitis, notably feces, dead tissues, barium, mucus, bile, and blood. 

Vasopressin levels are increased during hypotension to maintain blood pressure by vasoconstriction. However, there is a vasopressin deficiency in septic shock. Low doses of vasopressin increase MAP, leading to the discontinuation of vasopressors. However, routine use of vasopressin is not recommended because of lack of evidence of efficacy. Vasopressin is a direct vasoconstrictor without inotropic or chronotropic effects and may result in decreased cardiac output and hepatosplanchnic flow. Vasopressin use may be considered in patients with refractory shock despite adequate fluid resuscitation and high-dose vasopressors.24,27-28... 

Vascular Effects of Complement Activation. During complement activation a number of complement fragments (anaphylatoxins), which are polypeptides with inflammatory properties, are released. The anaphylatoxins C3a and C5a induce smooth muscle contraction and enhance vascular permeability (H31). The most pronounced activation of complement with the formation of anaphylatoxins and terminal C5-9 complexes has been observed in septic shock (B29, B30, P2). Studies indicate that there is a relation between high concentrations of anaphylatoxins and C5-9 complexes and the development of ARDS or MODS in patients with sepsis (H10). 

It has been shown that CGRP is released into the circulation during the development of human sepsis and septic shock (A8). Plasma CGRP levels correlated with the APACHE II score as well as with cardiac index and systemic vascular re-sistence index. There is also a relationship between the initial plasma CGRP levels and the severity of the disease at the time of admission to the ICU. Plasma CGRP levels are related to the hemodynamic changes seen early in septic shock. 

C5, Cannon, J. G Tompkins, R. G., and Gelfland, J. A., Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J. Infect. Dis. 161, 79-84 (1990). 

D20. Dinarello, C. A., Aiura, K., and Gelfland, J. A., The role of interleukin-1 in septic shock. In Yearbook of Intensive Care and Emergency Medicine (J.-L. Vincent, ed.) Springer-Verlag, Berlin, 25-35 (1992). 

M15. Massignon, D., Lepape, A., Bienvenu, J., Barbier, Y Boileau, C and Coeur, P Coagula-tion/fibrinolysis balance in septic shock related to cytokines and clinical state. Haemostasis 24, 36-48(1994). 

N5. Nava, E Palmer, M. J., and Moncada, S., Inhibition of nitric oxide synthesis in septic shock How much is beneficial . Lancet 338, 1555-1557 (1991). 

Ruokonen E., Takala J., Kari A., Saxen H., Mertsola J., Hansen E.J., Regional blood flow and oxygen transport in septic shock, Crit. Care Med. 1993 21 1296-1303. 

Corticosteroids were shown in a metaanalysis to improve hemodynamics and survival and reduce the duration of vasopressor support in septic shock. 

Corticosteroids can be initiated in septic shock when adrenal insufficiency is present or when weaning of vasopressor therapy proves futile. A daily dose equivalent to 200 to 300 mg hydrocortisone should be continued for 7 days. Adverse events are few because of the short duration of therapy. 

Receptor Activity of Cardiovascular Agents Commonly Used in Septic Shock... 

Beilman, G. J., Selective inducible nitric oxide synthase inhibition in septic shock, Crit. Care Med. 29 (2001), p. 2230-2231... 

Acute bloodstream infection Patients with underlying illness such as HIV, renal failure, and diabetes are affected by this type of the disease, which usually results in septic shock. The symptoms of the bloodstream infection vary depending on the site of original infection, but they generally include respiratory distress, severe headache, fever, diarrhea, development of pus-filled lesions on the skin, muscle tenderness, and disorientation. This is typically an infection of short duration, and abscesses will be found throughout the body. 

A medication order for a nine-month-old child weighing 8 kg includes dopamine in a dose of 5 mcg/kg/min. The drug available is dopamine 400 mg/5 mL. The physician ordered 70 mg of dopamine in 200 mL of D5W to be administered at 6.75 mL per hour to this child who is in septic shock. Check for the accuracy of the dilution order. 

An important practical goal in NOS research is the development of isoform-specific inhibitors (127). Diminished levels of NO contribute to chronic hypertensive diseases. In contrast, NO overproduction contributes to pathological conditions related to primary neurodegener-ative, inflammatory, and vascular disorders (5). In septic shock NOS... 

Prompt intensive treatment with corticosteroids may be lifesaving when an excessive inflammatory reaction has resulted in septic shock. A massive infusion of corticosteroids can restore cardiac output and reverse hypotension by sensitizing the response of adrenoceptors in the heart and blood vessels to the stimulating action of catecholamines. This protective role of steroids may be due to a direct effect on vascular smooth muscle. The combination of glucocorticoids and dopamine therapy preserves renal blood flow during shock. 

Keh, D., et al. (2003) Immunologic and hemodynamic effects of low-dose hydrocortisone in septic shock a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med. 167, 512-20. 

Endotoxaemia. - Exposure to bacterial endotoxin (lipopolysaccharide) can induce the production of pro-inflammatory mediators (e.g. tumour necrosis factor a and interleukin 1), culminating in septic shock profound vasodilation... 

A review of trials has suggested that vasopressin is more likely to cause adverse effects at doses of 0.04 U/minute or more when it is used to treat septic shock mesenteric ischemia and cardiac dysfunction and ischemia were particularly associated with high doses (30). The authors suggested that limiting the dosage to 0.03 U/minute may minimize these effects. This suggestion has been supported by a retrospective audit of the effects of continuous vasopressin infusion in septic shock in 102 men and women, mean age 53 years (31). There were adverse events that may have been linked to vasopressin in 18 patients cardiac arrest (n = 9) ischemic/mottled digits (n = 8) myocardial infarction (n = 1) and hyponatremia (n = 1). Adverse events occurred with doses of vasopressin of 0.04 units/minute and over, except in one patient (dose not stated). 

Further data have come from a review of the use of high doses of vasopressin (mean dose 0.47 U/minute) to replace noradrenaline (24). There were reductions in heart rate, cardiac index, and oxygen delivery. The authors recommended that the dose of vasopressin should not exceed 0.04 U/minute and that vasopressin should not be used as a single vasopressor agent in septic shock. 

Delmas A, Leone M, Rousseau S, Albanese J, Martin C. Clinical review vasopressin and terlipressin in septic shock patients. Crit Care 2005 9 212-22. 

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