sign in sign up
<<
Home , Inotrope, Permissive hypotension

Scholars Journal of Applied Medical Sciences (SJAMS) ISSN 2320-6691 (Online) Sch. J. App. Med. Sci., 2015; 3(2G):1027-1034 ISSN 2347-954X (Print) ©Scholars Academic and Scientific Publisher (An International Publisher for Academic and Scientific Resources) www.saspublisher.com

Review Article

Vasopressors and in : Which One to Choose? Sumit Pal Singh Chawla1*, Sarabjot Kaur2 1Sr. Resident, 2PG Resident, Department of Medicine, GGS Medical College & Hospital, Faridkot, Punjab, India

*Corresponding author Dr. Sumit Pal Singh Chawla Email: [email protected]

Abstract: Hemodynamic shock is a final common pathway associated with regularly encountered emergencies including , microbial , pulmonary embolism, significant trauma and anaphylaxis. Shock results in impaired tissue , cellular , and metabolic derangements that cause cellular injury. Prompt recognition and intervention are the cornerstones of mitigating the dire consequences of shock. The maintenance of end-organ perfusion is critical to prevent irreversible organ injury and failure, and this frequently requires the use of fluid and vasopressors and/or inotropes. Despite the widespread use of different vasopressors and inotropes in various types of shock, the understanding of their clinical effects is often inadequate and therefore, leads to erroneous therapeutic decision making. This article focusses on reviewing the underlying mechanisms of action of commonly employed vasopressors and inotropes, analysing published data on their clinical application in various types of shock, and finally, choosing the right vasopressor(s) and/or (s) in the management of various shock syndromes. Keywords: Shock, Vasopressors, Inotropes, Cellular hypoxia.

INTRODUCTION overlap between these categories, but determining Hemodynamic shock or circulatory shock is which form of shock is primarily involved, is helpful classically described as a life-threatening acute clinical for further definitive management. syndrome of inadequate blood perfusion to the tissues resulting in cellular injury and severe tissue dysfunction INITIAL THERAPY AND DIAGNOSTIC [1]. Although this early injury is often reversible, APPROACH persistent hypoperfusion leads to irreversible tissue As mentioned previously, once shock is recognized, damage, progressive organ dysfunction, and can certain immediate steps should be undertaken while the progress to death [2]. Prompt recognition and cause of shock is determined: intervention are the cornerstones of mitigating the dire  If the patient’s airway, oxygenation, or consequences of shock. Unlike other types of clinical ventilation is not effective, then the patient syndromes (e.g., chest pain), for which a clinical should be intubated. diagnosis is made before treatment is initiated in  Large-bore intravenous access should be earnest, the treatment of shock often occurs established. concurrently or ahead of the diagnostic process. The  Any arrhythmias should be addressed as per maintenance of end-organ perfusion is critical to the standard advanced cardiac life support prevent irreversible organ injury and failure, and this protocols. frequently requires the use of fluid resuscitation and  A trial of at least 1.0 L of crystalloid should be vasopressors and/or inotropes. Inotropes are agents infused to treat ; the fear of which can increase and should not preclude the use therefore (CO) whereas vasopressor of volume in a patient who is not perfusing agents increase vascular tone and thereby elevate mean adequately. In , this fluid arterial pressure (MAP). challenge will not be as harmful as compared to sustained hypotension [4]. The clinical manifestations and prognosis of  Vasopressors should only be initiated shock are largely dependent on the etiology and with/after adequate resuscitation is provided duration of insult. The most widely accepted with crystalloids, colloids, and/or blood classification system (Weil and Shubin classification products. Vasopressors are not recommended system) [3] organizes shock into four broad categories: in the initial stabilization of hemorrhagic shock (1) Hypovolemic, (2) Cardiogenic, (3) Obstructive, and [5]. may be employed (4) Distributive. Patients who are in shock often have 1027

Sumit Pal et al., Sch. J. App. Med. Sci., 2015; 3(2G):1027-1034

until is controlled in patients while other targeted diagnostic investigations requiring emergent surgical intervention [6]. In are ongoing. To summarise, the next steps for low cardiac output states, the use of an the diagnostic work-up for a patient who is in inotropic agent should be considered. shock should be as follows [4]:  The diagnosis of acute myocardial infarction (AMI), tension pneumothorax, cardiac  Complete blood count, complete serum tamponade, and massive pulmonary embolism biochemistry, serum lactate, arterial blood gas should be considered on the basis of the analysis, cardiac enzymes, electrocardiogram, available information. If any of these chest radiograph, random serum cortisol, and diagnoses is being considered, then targeted coagulation assessment. diagnostic and therapeutic interventions should  Echocardiogram, catheter, proceed while more formal diagnostic or an indwelling CO measurement. investigations occur concurrently. On the basis of the results of these investigations, Once the patient is stabilized, the the cause of shock can be ascertained. In general, in cause of shock can be safely assessed. In hypovolemic and , the patient is certain instances, the clinical situation may volume responsive. Volume responsive means that as point to an obvious cause, in which case the volume is infused, the (CI) increases treatment should be initiated for that cause of significantly. In case of hypovolemic shock, if the shock (e.g., antibiotics for ); volume is replaced faster than the volume being lost, however, given the myriad causes of shock, a then both (BP) and CI will increase structured diagnostic approach should still be proportionately. In patients with distributive shock, the conducted because of the ability of certain CI will respond significantly to volume, but the BP will types of shock to masquerade as one another often remain low as the hyperdynamic state evolves. and for multiple types of shock to coexist. The Usually, the CI will increase to a zenith, at which point key to distinguish distributive shock from volume no longer improves the CI yet the patient other categories of shock is an objective remains hypotensive, requiring the use of vasopressors. assessment of cardiac function. An If the patient’s CI is less than 2.0 despite volume echocardiogram, a pulmonary artery catheter, resuscitation, then obstructive or cardiogenic shock or an indwelling arterial line cardiac output must be considered [4]. assessment should be conducted as soon as possible. This cardiac assessment should occur

Table 1: Showing various types of shock and their common causes Types of Shock Common Causes 1. Hypovolemic Hemorrhage, vomiting, diarrhoea, burns, polyuria (), capillary leak causing "third spacing" 2. Cardiogenic Myocardial infarction, , drugs (e.g. overdose of beta blockers), valvular diseases, arrhythmias, 3. Obstructive Tension pneumothorax, pulmonary embolism, air embolism, cardiac tamponade, 4. Distributive - SIRS (Systemic inflammatory response syndrome) related: Sepsis, pancreatitis, trauma, burns - Neurogenic: Spinal cord injury - Endocrine related: Adrenal insufficiency, thyrotoxicosis - Anaphylactic - Liver failure

BRIEF REVIEW OF COMMON VASOPRESSORS (SVR) whereas activation of the α2 AND INOTROPES receptor reduces norepinephrine release at the synaptic Catecholamines end plate, thus mildly decreasing blood pressure and They can be endogenous (epinephrine, being mildly negatively . Activation of the norepinephrine, ) or synthetic (, β1 receptor, conversely, increases CO by its positive , phenylephrine). Cardiovascular effects of chrono-, dromo-, and inotropic actions, whereas these agents are mediated through their interaction with activation of the β2 receptor results in [7]. adrenergic and dopaminergic receptors. The four major Dopaminergic receptors (D1 and D2) are concentrated adrenergic receptors are α1, α2, β1 and β2 receptors. In in the kidney and splanchnic vasculature, and the cardiovascular system, activation of the α1 receptor stimulation of these leads to renal and mesenteric induces and increase in systemic vasodilatation. 1028

Sumit Pal et al., Sch. J. App. Med. Sci., 2015; 3(2G):1027-1034

The density and proportion of these receptors parameters of visceral microperfusion when are responsible for variations in the physiological hypotension is reversed in septic shock, compared with responses of inotropes and vasopressors in individual epinephrine or dopamine [16,17]. This may explain why tissues. Response of various vasopressor and inotropic norepinephrine therapy is associated with some survival agents is further modified by reflex autonomic changes benefit in septic shock, compared with high-dosage after acute BP alterations and effect of hypoxia or dopamine or epinephrine [18]. In comparison with acidosis on the binding affinities of these agents to epinephrine, norepinephrine demonstrates many fewer adrenergic receptors [8]. metabolic adverse effects. Coronary flow is increased owing to elevated diastolic blood pressure and indirect Epinephrine stimulation of cardiomyocytes, which release local Epinephrine or is a potent mixed α vasodilators [19]. Prolonged norepinephrine infusion and β adrenergic agonist. The β adrenergic effects are can have a direct toxic effect on cardiac myocytes by more pronounced at low doses and α adrenergic effects inducing apoptosis via activation and predominate at higher doses. Low dose of epinephrine increased cytosolic Ca2+ influx [20]. increases CO because of β1 receptor mediated inotropic and effects, while α1 receptor induced Dopamine vasoconstriction is often counterbalanced by β2 receptor Dopamine is an α and β adrenergic agonist that mediated vasodilation [9]. The result is an increased CO also stimulates dopaminergic receptors D1 and D2. The with decreased SVR and a variable effect on MAP. effects of dopamine are dose-dependent. At low doses However, at higher doses, α receptor mediated (1-3 μg/kg/min), it acts predominantly on D1 receptors vasoconstriction predominates which results in in the renal, mesenteric, cerebral and coronary vessels increased SVR in addition to increased CO. High and resulting in selective vasodilation. It is postulated that prolonged doses can cause direct cardiac toxicity dopamine increases urine output by augmenting renal through damage to arterial walls, which causes focal blood flow and glomerular filtration rate [21], however, regions of myocardial contraction band necrosis, and the clinical significance of “renal-dose” dopamine is through direct stimulation of myocyte apoptosis [10]. controversial because a renal protective effect has not Epinephrine can also cause tachyarrhythmia, lactic been conclusively demonstrated [21]. At intermediate acidosis, and hyperglycemia [11]. and doses (3-10 μg/kg/min), β1 adrenergic effect of hyperglycemia are caused by epinephrine induced dopamine predominates and results in increase in CO, hypermetabolism, suppression of release, and with variable effect on rate. At higher doses (10- glycolysis. In addition, epinephrine can compromise 20 μg/kg/min), α1 adrenergic effect of dopamine hepatosplanchnic perfusion, oxygen exchange, and predominates and results in vasoconstriction which lactate clearance, especially in septic shock [12,13]. In leads to an increase in SVR and MAP [7]. The α and β animal models, these adverse effects are dosage related adrenergic effects of dopamine are generally weaker and more pronounced as compared with norepinephrine compared with epinephrine or norepinephrine. or vasopressin [12,13]. Dopamine is used as a vasoconstrictor in and as an inotrope in low CO states. Dopamine’s Epinephrine is the first-line catecholamine in niche indication is vasodilatory shock associated with cardiopulmonary resuscitation and anaphylactic shock. , both of which can be corrected with this As a vasopressor and as an inotrope, it is usually agent. Despite the theoretical beneficial effect of considered a second-line agent. dopamine on splanchnic perfusion by stimulation of D1 receptors, this has not been reproduced in critically ill Norepinephrine patients. Published data in sepsis suggest that dopamine

Norepinephrine or noradrenaline has potent α1 may impair hepatosplanchnic perfusion and metabolism and modest β adrenergic effects which render it a [22,23,24]. Tachycardia, another adverse effect of powerful vasoconstrictor with less potent direct dopamine, together with vasoconstriction can lead to inotropic properties [14]. It has minimal chronotropic increased cardiac oxygen demand and decreased effects because of which it is a drug of choice in oxygen delivery and may trigger myocardial settings where stimulation is undesirable. and arrhythmias [24]. Because of its marked vasoconstrictive characteristics, norepinephrine seems the logical drug of choice in Dobutamine distributive forms of shock by increasing MAP, Dobutamine is a synthetic catecholamine with effective circulating , and thus venous predominant β adrenergic and only limited α adrenergic return and , with minimal increase of heart rate effects. As a result of β1 receptor mediated positive or . It is more potent than dopamine and inotropic, and β2 receptor mediated vasodilatory action, is commonly considered the first-choice vasopressor to dobutamine increases CO and decreases systemic and reverse hypotension in vasodilatory shock [15]. Some pulmonary vascular resistance. Dobutamine is the clinicians fear that the use of norepinephrine will cause preferred vasoactive agent to treat cardiogenic shock severe vasoconstriction in visceral and renal with low output and increased . In combination microvasculature, yet norepinephrine seems to improve with norepinephrine, dobutamine is used in septic shock

1029

Sumit Pal et al., Sch. J. App. Med. Sci., 2015; 3(2G):1027-1034 with myocardial dysfunction. α1 receptor mediated may limit its utility in clinical conditions in which vasoconstriction progressively dominates at higher induction of ischemia is potentially harmful. Tolerance dosages [25]. Despite its mild chronotropic effects at can develop after just a few days of therapy [27], and low to medium doses, dobutamine significantly malignant ventricular arrhythmias can be observed at increases myocardial oxygen consumption [26]. This any dose.

Table 2: Commonly used Vasopressor and Inotropic Drugs - Indication, Dose, Receptor binding, Side effects Adrenaline Noradrenaline Dopamine Dobutamine Clinical Cardiogenic, Septic, Septic, Cardiogenic, Cardiogenic, Septic Low CO Indication Anaphylactic shock, Vasodilatory shock shock (Cardiogenic shock, Cardiac arrest Sepsis induced myocardial dysfunction) Dose Infusion: 0.01-0.1 0.01-3 μg/kg/min 2-20 µg/kg/min 2-20 μg/kg/min μg/kg/min, Bolus: 1 mg IV every 3- 5 min (max: 0.2 mg/Kg), IM: (1:1000): 0.1-0.5 mg (max 1 mg) Receptor binding α1 +++++ +++++ +++ + β1 ++++ +++ ++++ +++++ β2 +++ ++ ++ +++ DA N/A N/A +++++ N/A Major Side Arrhythmias, Cardiac Arrhythmias, Arrhythmias, Tachycardia, effects ischemia, Sudden Bradycardia, Digital Cardiac ischemia, arrhythmias, cardiac death, ischemia, , Cardiac ischemia Hypertension Hypertension Tissue ischemia/gangr-ene

Phenylephrine associated with relative deficiency of vasopressin. Phenylephrine is a potent α1 adrenergic agonist Exogenous administration of vasopressin reverses with virtually no affinity for β adrenergic receptors. It is vasodilation in vasopressor-resistant shock by commonly used as a rapid bolus for immediate activation of V1 receptors, inhibition of ATP-sensitive correction of sudden severe hypotension until more potassium channels [28], attenuation of nitrous oxide definitive therapies are instituted. It can be used to raise production [29], and amplification of vasoconstrictive MAP in patients with severe hypotension and catecholamine effect [30]. Vasopressin is a second-line concomitant aortic stenosis, to correct hypotension agent in septic shock or refractory hypotension that is caused by simultaneous ingestion of sildenafil and unresponsive to norepinephrine (or epinephrine). nitrates, to decrease the outflow tract gradient in Furthermore, the pressor effects of vasopressor are patients with obstructive hypertrophic cardiomyopathy, relatively preserved during hypoxic and acidotic and to correct vagally mediated hypotension during conditions, which commonly develop during shock of percutaneous diagnostic or therapeutic procedures. This any origin. agent has virtually no direct effect on heart rate; although it has the potential to induce significant OPTIMAL SELECTION OF VASOPRESSORS baroreceptor mediated reflex rate responses after rapid AND INOTOPES IN VARIOUS TYPES OF alterations in MAP [7]. SHOCK Hemorrhagic Shock Vasopressin Vasopressors are rarely indicated and should Vasopressin or “antidiuretic hormone” exerts be considered only when volume replacement is its circulatory effects through V1 receptors on vascular complete, haemorrhage is arrested and hypotension smooth muscles and V2 receptors on renal collecting continues [5]. Permissive hypotension is evolving as a duct system. V1 receptor stimulation mediates treatment strategy in which the goal is to keep the blood vasoconstriction whereas V2 receptor activation pressure low enough to avoid exsanguination but mediates water reabsorption by enhancing renal maintain perfusion of end organs [6]. Early vasopressor collecting duct permeability. Overall, vasopressin tends use within the first 24 hours in patients not to cause increase in SVR. Vasopressin modulated appropriately resuscitated with blood products and increase in vascular sensitivity to noradrenaline further fluids has been suggested to increase the risk of augments its vasopressor effect. Septic shock is mortality [31]. 1030

Sumit Pal et al., Sch. J. App. Med. Sci., 2015; 3(2G):1027-1034

possible dose and for minimum period of time is most Cardiogenic Shock appropriate. Inotropes and vasopressors, when used in the setting of cardiogenic shock complicating AMI, can Numerous studies have been suggestive of increase myocardial oxygen consumption and can cause some advantage of norepinephrine and dopamine over ventricular arrhythmias, contraction-band necrosis, and epinephrine [15,18]. Septic patients may have low, infarct expansion. However, critical hypotension itself normal, or increased cardiac output. Therefore, compromises myocardial perfusion, leading to elevated treatment with a combined inotrope/vasopressor, such left ventricular (LV) filling pressures, increased as noradrenaline or dopamine, is recommended if myocardial oxygen requirements, and further reduction cardiac output is not measured. As per the Surviving in the coronary perfusion gradient. Thus, hemodynamic Sepsis Campaign guidelines [35], norepinephrine is benefits usually outweigh specific risks of inotropic more potent than dopamine and may be more effective therapy when used as a bridge to more definitive at reversing hypotension in septic shock. A meta- treatment measures. The lowest possible doses of analysis of dopamine versus norepinephrine in the inotropic and pressor agents should be used to treatment of septic shock also concluded that dopamine adequately support vital tissue perfusion while limiting administration is associated with greater mortality and a adverse consequences. The American College of higher incidence of arrhythmia events [36]. Cardiology/American Heart Association (ACC/AHA) guidelines for ST-elevation myocardial infarction In hyperdynamic septic shock, during which (STEMI) recommend the selection of vasopressor urine flow is believed to decrease mainly because of and/or inotrope therapy based on systolic blood lowered renal glomerular perfusion pressure, the use of pressure (SBP) plus the presence or absence of signs norepinephrine markedly improves MAP and and symptoms of shock [32]. For patients with a SBP of glomerular filtration. After restoration of systemic 70-100 mm Hg, dobutamine is recommended in the , urine flow reappears in most patients absence of shock and dopamine if shock is present. and renal function improves. This fact supports the Norepinephrine is recommended when SBP is <70 hypothesis that the renal ischemia observed during mmHg. However, the results of a multicenter, hyperdynamic septic shock is not worsened by randomized trial conducted in 2010 by De Backer et al norepinephrine infusion and even suggests that this challenged the recommendation of dopamine as a first drug may be effective in improving renal blood flow line vasopressor agent over norepinephrine in and renal vascular resistance [37-40]. cardiogenic shock patients. The trial was conducted to determine if the use of norepinephrine over dopamine In 2008, the VAAST trial compared as the first line vasopressor agent could reduce the rate norepinephrine plus vasopressin to norepinephrine of death among patients in shock [33]. Although no alone in the treatment of septic shock and found no difference was found in the primary outcome of 28-day difference in 28-day mortality rates or overall rates of mortality, a subgroup analysis found a higher mortality serious adverse events [41]. Dobutamine may be rate in cardiogenic shock patients who received initiated in combination with norepinephrine in patients dopamine. The exact cause of this increased mortality with myocardial dysfunction (i.e. elevated cardiac could not be determined. Moderate doses of filling pressure, low CO) alongwith septic shock [34]. combination of may be more effective than maximal doses of any individual . The latest recommendations of Surviving Sepsis Dobutamine may be initiated in combination with Campaign (revised in 2012) regarding use of norepinephrine in cardiogenic shock and thus reduce vasopressor(s) and/or inotrope(s) in septic shock are as the side effects associated with high doses of each drug. follows [42]:  Adequate fluid resuscitation is a prerequisite Septic Shock for the successful and appropriate use of Septic shock results when infectious agents or vasopressors in patients with septic shock. infection-induced mediators in the bloodstream produce When an appropriate fluid challenge fails to hemodynamic decompensation. Its pathogenesis restore an adequate arterial pressure and organ involves a complex interaction among pathologic perfusion, therapy with vasopressor agents vasodilation, increased capillary permeability, relative should be started. Vasopressor therapy may and absolute , myocardial dysfunction, and also be required transiently to sustain life and altered blood flow distribution due to the inflammatory maintain perfusion in the face of life- response to infection [34]. When fluid administration threatening hypotension, even when fails to restore an adequate arterial pressure and organ hypovolemia has not been resolved or when a perfusion in patients with septic shock, therapy with fluid challenge is in progress. vasopressor(s) with or without inotrope(s) should be  Apply Vasopressor(s) to maintain MAP ≥65 initiated to achieve the desired physiological target. The mm Hg. use of vasopressor and inotropic agents in the lowest  Norepinephrine is the first choice vasopressor agent to correct hypotension in septic shock. 1031

Sumit Pal et al., Sch. J. App. Med. Sci., 2015; 3(2G):1027-1034

 Epinephrine (added to and potentially shock can occur at any time, from initial presentation to substituted for norepinephrine) may be used several weeks post injury [46]. The primary treatment when an additional agent is needed to maintain for is fluid resuscitation. If there is adequate BP. inadequate response to fluid resuscitation, vasopressors  Vasopressin 0.03 units/minute can be added to with alpha and beta activity such as norepinephrine norepinephrine with intent of either raising should be initiated to counter the loss of sympathetic MAP or decreasing norepinephrine dosage. tone and provide chronotropic cardiac support [45].  Low dose vasopressin is not recommended as the single initial vasopressor for treatment of CONCLUSION sepsis-induced hypotension and vasopressin There are only a few studies that provide evidence doses higher than 0.03-0.04 units/minute for a particular vasopressor or inotropic strategy in the should be reserved for salvage therapy (failure early management of shock. Most recommendations for to achieve adequate MAP with other vasoactive strategies are largely based on vasopressor agents). pharmacodynamic modeling, animal research, empirical  Dopamine may be used as an alternative experience, and limited human trials performed in a vasopressor agent to norepinephrine only in critical care environment. Despite these limitations, a highly selected patients (e.g., a patient with basic knowledge of the available evidence and a better low risk of tachyarrhythmias and absolute or understanding of the actions, limitations and side effects relative bradycardia). Dopamine increases of individual vasoactive agent can help guide a MAP primarily by increasing CI with minimal physician to tailor therapy to specific patient effects on SVR. presentations.  Low-dose dopamine should not be used for renal protection. The vasopressors or inotropes should be used  The combination of norepinephrine and in the minimum possible dose and should be kept in a dobutamine seems to be more predictable and supportive context to allow treatment of the underlying more appropriate to the goals of septic shock disorder. Smaller combined doses of inotropes and therapy than norepinephrine with dopamine or vasopressors may be advantageous over a single agent dopamine alone. A trial of dobutamine used at higher dose to avoid dose-related adverse infusion may be administered or added to effects. vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac Norepinephrine is considered the first-line filling pressures and low CO, or (b) ongoing vasopressor in vasodilatory shock especially septic signs of hypoperfusion, despite achieving shock, dobutamine the first-line inotrope in shock adequate intravascular volume and adequate associated with decreased cardiac output, and their MAP. combination in vasodilatory shock with decreased cardiac output. In cardiogenic shock complicating AMI,  Phenylephrine is not recommended in the current guidelines based on expert opinion recommend treatment of septic shock except in dobutamine as the first-line agent for moderate circumstances where (a) norepinephrine is hypotension (systolic blood pressure 70 to 100 mm Hg) associated with serious arrhythmias, (b) and norepinephrine as the preferred therapy for severe cardiac output is known to be high and BP persistently low or (c) as salvage therapy when hypotension (systolic blood pressure <70 mm Hg). combined inotrope/vasopressor drugs and low Epinephrine is the first-line catecholamine in dose vasopressin have failed to achieve MAP cardiopulmonary resuscitation and anaphylactic shock, target. and can also be used as a second line agent in shock that is unresponsive to other catecholamines. Vasopressin is emerging as a therapy in resistant Anaphylactic Shock Adrenaline is the treatment of choice for vasodilatory shock. The use of other catecholamines anaphylaxis. The recommended dose is 0.3 to 0.5 mg and modern nonadrenergic vasoactive drugs in shock (concentration of 1:1000) intramuscularly (IM) every 5 remains with little evidence. In general, results of large, to 10 minutes for adults [43]. Intravenous epinephrine is high-quality trials of catecholamines and vasoactive reserved for cases of cardiovascular collapse or those agents for shock are urgently required to provide data who fail to respond to IM therapy [44]. for evidence-based guidelines for their use.

Neurogenic Shock REFERENCES 1. Jimenez E; Shock. In Civetta JM, Taylor RW, Neurogenic shock most often occurs in rd patients with severe spinal cord injury at the cervical or Kirby RR editors; Critical Care, 3 edition, high thoracic level [45]. A shock state occurs as a result Lippincott Williams & Wilkins, Philadelphia, of sympathetic denervation leading to reduced 1997: 359-387. sympathetic outflow to the cardiovascular system and 2. Mitchell RN; Shock. In Kumar V editor; subsequent decreased CO and SVR [46]. Neurogenic Robins and Cotran: Pathologic Basis of 1032

Sumit Pal et al., Sch. J. App. Med. Sci., 2015; 3(2G):1027-1034

Disease 6th edition, Saunders, Philadelphia, 16. Ledoux D, Astiz ME, Carpati CM, Rackow 2005: 134-138. EC; Effects of perfusion pressure on tissue 3. Weil MH, Shubin H; Proposed reclassification perfusion in septic shock. Crit Care Med., of shock states with special reference to 2000; 28(8): 2729-2732. distributive effects. In Hinshaw LB, Cox BG 17. Marik PE, Mohedin M; The contrasting effects editors; The Fundamental Mechanisms of of dopamine and norepinephrine on systemic Shock. 1st edition, Plenum Press, New York, and splanchnic oxygen utilization in 1972: 13-23. hyperdynamic sepsis. JAMA, 1994; 272(17): 4. Rosenthal SF, Saner F, Chawla LS; Approach 1354-1357. to hemodynamic shock and vasopressors. Clin 18. Martin C, Viviand X, Leone M, Thirion X; J Am Soc Nephrol., 2008; 3(2): 546-53. Effect of norepinephrine on the outcome of 5. Martel MJ, MacKinnon KJ, Arsenault MY, septic shock. Crit Care Med., 2000; 28(8): Bartellas E, Klein MC; Hemorrhagic shock. J 2758-2765. Obstet Gynaecol Can., 2002; 24(6): 504-520. 19. Tune JD, Richmond KN, Gorman MW, Feigl 6. Duchesne JC, McSwain NE, Cotton BA; EO; Control of coronary blood flow during Damage control resuscitation: The new face of exercise. Exp Biol Med (Maywood), 2002; damage control. J Trauma, 2006; 69(4): 976- 227(4): 238-250. 990. 20. Communal C, Singh K, Pimentel DR, Colucci 7. Tabaee A, Givertz MM; Pharmacologic WS; Norepinephrine stimulates apoptosis in management of the hypotensive patient. In adult rat ventricular myocytes by activation of Irwin RS, Rippe JM editors; Irwin and Rippe’s the α-adrenergic pathway. Circulation, 1998; . 5th edition, 98: 1329-34. Lippincott Williams & Wilkins, Philadelphia, 21. Bellomo R, Chapman M, Finfer S, Hickling K, 2003: 295-302. Myburgh J; Low dose dopamine in patients 8. Overgaard CB, Dzavík V; Inotropes and with early renal dysfunction: a placebo- vasopressors: Review of physiology and controlled randomised trial - Australian and clinical use in cardiovascular disease. New Zealand Intensive Care Society Circulation, 2008; 118: 1047-1056. (ANZICS) Clinical Trials Group. Lancet, 9. Jones CJ, DeFily DV, Patterson JL, Chilian 2000; 356(9248): 2139-2143. WM; Endothelium-dependent relaxation 22. Guerin JP, Levraut J, Samat LC, Leverve X, competes with α1- and α2-adrenergic Grimaud D, Ichai C; Effects of dopamine and constriction in the canine epicardial coronary norepinephrine on systemic and microcirculation. Circulation, 1993; 87: 1264- hepatosplanchnic hemodynamics, oxygen 1274. exchange, and energy balance in vasoplegic 10. Singh K, Xiao L, Remondino A, Sawyer DB, septic patients. Shock, 2005; 23(1): 18-24. Colucci WS; Adrenergic regulation of cardiac 23. Martin C, Viviand X, Leone M, Thirion X; myocyte apoptosis. J Cell Physiol, 2001; Effect of norepinephrine on the outcome of 189(3): 257-265. septic shock. Crit Care Med., 2000; 28(8): 11. Trager K, DeBacker D, Radermacher P; 2758-2765. Metabolic alterations in sepsis and vasoactive 24. Debaveye YA, Van den Berghe GH; Is there drug-related metabolic effects. Curr Opin Crit still a place for dopamine in the modern Care, 2003; 9(4): 271-278. ? Anesth Analg, 2004; 12. De Backer D, Creteur J, Silva E, Vincent JL; 98(2): 461-468. Effects of dopamine, norepinephrine, and 25. Ruffolo RR; The pharmacology of epinephrine on the splanchnic circulation in dobutamine. Am J Med Sci., 1987; 294(4): septic shock: Which is best? Crit Care Med., 244-248. 2003; 31(6): 1659-1667. 26. Patel RN, Arteaga RB, Mandawat MK, 13. Meier AH, Reinhart K, Bredle DL, Specht M, Thornton JW, Robinson VJ; Pharmacologic Spies CD, Hannemann L; Epinephrine impairs stress myocardial perfusion imaging. South splanchnic perfusion in septic shock. Crit Care Med J., 2007; 100(10): 1006-1014. Med., 1997; 25(3): 399-404. 27. Unverferth DA, Blanford M, Kates RE, Leier 14. Bangash MN, Kong ML, Pearse RM; Use of CV; Tolerance to dobutamine after a 72 hour inotropes and vasopressor agents in critically continuous infusion. Am J Med., 1980; 69(2): ill patients. Br J Pharmacol., 2012; 165(7): 262-266. 2015-2033. 28. Salzman AL, Vromen A, Denenberg A, Szabo 15. Martin C, Papazian L, Perrin G, Saux P, Gouin C; K+ (ATP)-channel inhibition improves F; Norepinephrine or dopamine for the hemodynamics and cellular energetics in treatment of hyperdynamic septic shock? hemorrhagic shock. Am J Physiol., 1997; Chest, 1993; 103(6): 1826-1831. 272(2 Pt 2): H688-694.

1033

Sumit Pal et al., Sch. J. App. Med. Sci., 2015; 3(2G):1027-1034

29. Kusano E, Tian S, Umino T, Tetsuka T, Ando 41. Russell JA, Walley KR, Singer J; Vasopressin Y, Asano Y; Arginine vasopressin inhibits versus norepinephrine infusion in patients with interleukin-1 beta-stimulated nitric oxide and septic shock. N Engl J Med, 2008; 358(9): cyclic guanosine monophosphate production 877-87. via the V1 receptor in cultured rat vascular 42. Dellinger RP, Levy MM, Rhodes A; Surviving smooth muscle cells. J Hypertens., 1997; Sepsis Campaign: International guidelines for 15(6): 627-632. management of severe sepsis and septic shock: 30. Hamu Y, Kanmura Y, Tsuneyoshi I, 2012. Crit Care Med, 2013; 41: 580-637. Yoshimura N; The effects of vasopressin on 43. Tupper J, Visser S; Anaphylaxis: A review and endotoxin-induced attenuation of contractile update. Can Fam Physician, 2010; 56(10): responses in human gastroepiploic arteries in 1009-1011. vitro. Anesth Analg, 1999; 88(3): 542-548. 44. Sampson H, Munoz AF, Campbell RL, 31. Sperry JL, Minei JP, Frankel HL; Early Use of Adkinson NF, Bock SA, Branum A et al.; Vasopressors after injury: Caution before Second symposium on the definition and constriction. J Trauma, 2008; 64(1): 9-14. management of anaphylaxis: summary report - 32. Antman EM, Anbe DT, Armstrong PW; Second National Institute of Allergy and ACC/AHA Guidelines for the Management of Infectious Disease/Food Allergy and Patients with ST-Elevation Myocardial Anaphylaxis Network symposium. J Allergy Infarction: A Report of the American College Clin Immunol., 2006; 117(2): 391-397. of Cardiology/American Heart Association 45. Furlan JC, Fehlings MG; Cardiovascular Task Force on Practice Guidelines (Committee complications after acute spinal cord injury: to Revise the 1999 Guidelines for the Pathophysiology, diagnosis, and management. Management of Patients with Acute Neurosurg Focus, 2008; 25(5): E13. Myocardial Infarction). Circulation, 2004; 46. McMahon D, Tutt M, Cook AM; 110(9): 282-92. Pharmacological management of 33. De Backer D, Biston P, Devriendt J, Madl C, hemodynamic complications following spinal Chochrad D; Comparison of dopamine and cord injury. Orthopedics, 2009; 32(5): 331. norepinephrine in the treatment of shock. N Engl J Med., 2010; 362: 779-89. 34. Dellinger RP; Cardiovascular management of septic shock. Crit Care Med., 2003; 31(3): 946-955. 35. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R et al.; Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med, 2008; 36(1): 296-327. 36. De Backer D, Aldecoa C, Njimi H, Vincent JL; Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med, 2012; 40(3): 725-730. 37. Redl-Wenzl EM, Armbruster C, Edelmann G; The effects of norepinephrine on hemodynamics and renal function in severe septic shock states. Intensive Care Medicine, 1993; 19(3): 151-154. 38. Fukuoka T, Nishimura M, Imanaka H; Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels. Critical Care Medicine, 1989; 17(11): 1104-1107. 39. Martin C, Eon B, Saux P; Renal effects of norepinephrine used to treat septic shock patients. Critical Care Medicine, 1990; 18(3): 282-285. 40. Desjars P, Pinaud M, Bugnon D; Norepinephrine therapy has no deleterious renal effects in human septic shock. Crit Care Med., 1989; 17(5): 426-429.

1034