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First Line Choice of Pressors - Is there a difference?

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Ray Sutkowski

on 8 January 2013

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Transcript of First Line Choice of Pressors - Is there a difference?

Ray Sutkowski, M.D.
Scholarly Project What are the experts saying? So, what will it be? ....the answer may (or may not) be SHOCKing Norepinephrine 1. "Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study," by Yasser, et al. 2006. -Overall, there is appreciable statistical difference in 28 day mortality, as initially questioned, depending on type of shock.
-Additionally, there are physiologic and safety significances to choose NE as your initial vasopressor (unless, obviously, you're facing hypovolemic shock.
-Produces less tachycardia
-Not particularly arrhythmogenic
-Increases cardiac index (except for hypovolemic shock)
-More effective and has better outcomes than DA
-seen particularly in MAP and CI of septic pts who had received DA and fluids
-Splanchnic perfusion and gut mucosal perfusion
-Decreased serum lactate Is there a difference between Dopamine and Norepinephrine? References 1. Longo, Dan, et al. Harrison's Principles of Internal Medicine, 18th Ed, 2012. 2. Marino, Paul. The Little ICU Book. 2009 3. Ramachandran, Anand. Pharmacology Recall. 2007 4. De Backer, Daniel, et al. "Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis." Crit Care Med. Vol 40, No 3, 2012 5. Coxford, Nathan, Lang, E., Dowling, S. "Dopamine versus norepinephrine in the treatment of shock." CJEM Journal Club. 13(6): 395-397, 2011 6. De Backer, Daniel, et al. "Dopamine and norepinephrine in the Treatment of Shock." N Engl J Med, 2010: 362: 779-789. March 4, 2010 7. Patel, Gourang, et al. "Efficacy and Safety of DopamineVersus Norepinephrine in the Management of Septic Shock. SHOCK, Vol 33, No4, pp. 375-380. 2010 8.Vincent, J.L, et al. "Dopamine versus norepinephrine: is one better?" Minerva Anestheiologica, Vol 75, No 5, pp. 333-7. 2009 9. Sakr, Yasser, et al. "Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study." Crit Care Med, Vol 34, No 3, 2006. 10. Sharma, V., Dellinger, R. "The International Sepsis Forum's controversies in sepsis: my initial vasopressor agent in septic shock is norepinephrine rather than dopamine." Crit Care, 7(1): 3-5. 2003 Clinical Scenario: Overview Dopamine -Precursor to NE and works on CNS
-DA1, DA2, Beta 1/2, alpha 1 - dose dependent
-Ionotropic + Chronotropic + Inc BP
-Support of vascular resistance in those
whose BP cannot handle increased SVR

Pros: Can be given through peripheral IV,
Iono/Chronotrophic support, increased CO,
increased diaphragmatic function and
resorption of edematous fluid (pul ed and CHF), inc splanchnic flow

Cons: Decreased GH & Prolactin, tachycardia, arrhythmia,
extravasation necrosis, dec flow to gut mucosa Shock -Inadequate tissue perfusion leading to cellular dysfn.
-Maldistribution of bloodflow -->Multiple Organ Failure.
-Skin mottling, decreased CO, SBP <90 after fluids, MAP <60.
-After initial fluid resuscitation, vasopressor use to achieve and maintain adequate BP and organ perfusion is cornerstone is hemodynamic support..... -Endogenously produced by adrenal medulla
-Direct binding agent, no conversion
-alpha 1/2 >> beta 1
-Vasoconstriction and ionotropic response

Pros: Inc gut mucosa flow (leads to inc pH) , mild reflex bradycardia, very effective in restoring hemodynamic stability, newer studies show inc in UOP, shown quicker reversal - pts able to wean faster vs DA.

Cons: Central line needed, not widely accepted in hypovolemic shock 2/2 vasocontriction, high peripheral
vasoconstriction - necrosis -B.T., 67y/o/f, with PMH most significant for Anxiety, HTN/CAD with previous stent of LAD, and Rhematoid Arthritis on "long-term" Ranexa and MTX presented to the ED on 10/10/12 with 2 week history of nonproductive cough, increased SOB and DOE. Afebrile, no constitutional symptoms. Never a smoker. Had not received MTX or Remicade in 2-3 weeks 2/2 illness. -Seen by her PCP 3 days earlier, CXR suspicious for PNA, started on Levaquin and Tessalon Pearles. However, cough worsened and now post-tussive emesis. In the ED - Tmax: 97.7, 112/52, 78, 18, 100% on RA. CXR - prominent interstitial markings in b/l UL & LL, no focal consolidation, effusion, pna.
IV Access: PICC, as pt was "hard stick."
Lab: Cr 1.19 with CrCl 35, baseline Cr 1.01
PE: significant only for 2-3/6 systolic murmur in LUSB.
Admitted patient for CAP vs Atypical PNA and AKI on CKD III- Rocephin, Zithromax, DuoNeb, Pulm rehab, resp protocol, IVF, recheck labs, CT chest. Progression: 10/10: CT chest w/o - b/l patchy PNA, extensive interstital changes
10/11: Tmax 100.1, increased pain 2/2 RA, started steroid after speaking w/Rheum. Consulted Drs. Ali and Weinstein. Agree with Abx and thoughts to bronch. TB check, viral panels. Never febrile or WBC. 10/12: uncontrolled cough, desat to mid 70s with respiratory in room, put on high flow nasal cannula. 10/13: Still on high flow O2, desat, increased anxiety, tolerated BAL 10/14: increased anxiety, hyperventilating, desat into low 70s, 15L high flow, BP 117/52, RR 22, afebrile, no leukocytosis. Creatinine 1.03. 10/14 night -early morning 10/15: RR 20s, SBP 68. Now what? 10/15: call: SBP 60s, Bolus. Go to room, mottled, brady, hypotensive, unresponsive, NRB mask. ACLS. Atropine, Epi, compressions, ROSC, etomidate, ETT, go to MSICU. Becomes hypotensive...... -Cohort, multiple-center, observational study.
-3,147 pts in 198 ICUs, 1058 had shock at any time, 462 had septic shock.
-Considered 30d survival as primary outcome, and p < 0.05 was significant.
-NE was used in 80.2% and DA 35.4% as single agents.
-Age, gender, and SOFA score were comparable between groups

CONCLUSION: DA group had higher ICU (42.9% vs 35.7%, p=0.02) and hospital (49.9% vs 41.7%, p=0.01) mortality rates. 2. "Dopamine versus norepinephrine: is one better? " J.-L. VINCENT, et al, Brugmann Hospital, Université libre de Bruxelles, Brussels, Belgium. 2009 -Renal System: Meta-analysis by PF Marik in 2002 concluded that there was no beneficial effect of low-dose DA, and might in fact be responsible for renal cortex ischemia.

-GI system: Low dose DA can increase global splanchnic blood flow and oxygenation, but does not improve mucosal blood flow. Studies by Schmidt, et al, and Giraurd et al was shown to have increased lactic acid levels and precipitate gut ischemia in animal models.

-CNS: DA decreases prolactin, which is an immunoregulatory hormone, provoking transient reduction in T-cell response and lymphocyte count**

-NE vs DA in shock states - DA normalized hemodynamics in 31%, while NE was successful in 93% in septic shock. 3. "Efficacy and Safety of Dopamine versus Norepinephrine in the Management of Septic Shock." GP Patel, et al. Rush University Medical Center. SHOCK, Vol 33, No 4, 2010 -Prospective, randomized, open-label, clinical trial in MICU at Rush Univ. in 252 fluid resuscitated adult pts in septic shock.
-Evaluated the efficacy & safety of NE and DA as initial vasopressor in septic shock, with 28 day mortality as the primary endpoint. Considered p<0.05 significant

-Identified APACHE II score (p<0.001) and arrhythmia (p<0.015) as significant predictors of outcome.
-28-day mortality rate was 50% (67/134) with DA and 43% (51/118) for NE (p=0.282)
-Greater incidence of sinus tachy with DA (24.6%) vs NE (5.9%) and greater incidence of arrhythmias with DA (19.4%) vs NE (3.4%, p<0.0001).
-"renal dose" DA was associated with increased arrhythmia.

CONCLUSION: DA and NE were equally effective as initial agents as judged by 28-day mortality rates. However, DA was associated with significantly more cardiac arrhythmias 4. "Comparison of Dopamine and Norepinephrine in the Treatment of Shock" De Backer, et al. NEJM 362: 779-789, March 4, 2010 -Multicenter, randomized trial, 1679 pts, of whom 858 assigned to DA, and 821 to NE, between Dec 19, 2003 - Oct 6, 2007 with 28 day mortality as primary outcome.
-Eval whether choice of NE over DA as first-line vasopressor could reduce rate of death among pts in shock.*
-Used APACHE II for admission and SOFA score for mortality risk and progression
-No significant differences between the groups in regard to baseline characteristics*

-More pts in the DA group required open-label NE therapy at some point (26%, p<0.001), Mean time to achievement of MAP of 65mmHg was similar (6.3 +/- 5.6hrs in DA and 6.0 +/- 4.9 hrs in NE), increase in HR > with DA, death from refractory shock occurred more frequently in the DA group (p=0.05), 309 had arrhythmia with a. fib being most common (86.1%).

CONCLUSION: No significant difference in rate of death at 28 days between patients who received DA and those who received NE.
-HOWEVER, this is not true with predefined subgroup (i.e. septic shock or cardiogenic shock, p=0.03)
-Study raised serious concerns about the safety of DA therapy, as it is associated with more arrhythmias and increased rate of death in subgroups of patients. 5. "Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis." De Backer, et al. Crit Care Med, Vol 40, No. 3, 2012 -Evaluate the effects of NE and DA on outcome and adverse events in patients with septic shock with 28-day mortality used as primary outcome, p<0.05 considered significant.
-5 Observational (1,360 pts) and 6 Interventional/Randomized (1,408 pts) trials, totaling 2,768 pts.

-Obs studies: significant heterogeneity which yielded no appreciable difference. Excluding heterogeneous trial(s) - DA was associated with increased risk of death (RR 1.23, p<0.01).
-Interv studies: Aggregate RR of death with DA was significantly higher than with NE use (RR 1.12, p=0.35).
-Significant increase in arrhythmic events in the DA treated pts.
-No difference in LOS in ICU between groups receiving either pressor.
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