Jacob B. Keeperman, MD

Assistant Professor of Anesthesiology and Emergency Medicine Department of Anesthesiology, Division of Critical Care Medicine

Division of Emergency Medicine, Section of EMS Washington University School of Medicine

Saint Louis, Missouri

Medical Director Air Evac Lifeteam

Disclosures

•  I have no financial disclosures to report.

Vasopressor of Choice for Septic Shock

Targets for Vasopresor Therapy

Clinical Application

What we will cover…

What pressor does your agency carry?

Patient Characteristics

Effects on Regional Vascular

Beds

Clinical Trial Results

What is the vasopressor of choice for septic shock?

BP= CO x SVR

Pulmonary hypertension? ARDS? HOCM? EF 20%? Cardiac valves? Perioperative MI? Mesenteric ischemia?

HYPOVOLEMIC

§ Capillary leak (exacerbated by venodilation) § Poor cardiac filling

DISTRIBUTIVE

Macrovascular: § Arterial hypotension § Shunting to “vital” organs § Regional hypoperfusion

Microvascular: § Vasodilation § Precapillary shunting § Impaired microvascular flow § Microvascular thromboses

Mitochondrial dysfunction: § Impaired oxygen utilization § “Cytopathic hypoxia”

Patient Characteristics

Effects on Regional Vascular

Beds

Clinical Trial Results

What is the vasopressor of choice for septic shock?

Clinical Trials & Outcome data. Do we have any?

Effect of norepinephrine on the outcome of septic shock Martin et al, Crit Care Med 2000

Mortality Rates (%)

Time Period Dopamine NE Odds Ratio P Value

ICU 50.2 45.9 1.19 0.07

Hospital 59.4 56.6 1.12 0.24

28 Days 52.5 48.5 1.17 0.10

6 Month 63.8 62.9 1.06 0.71

12 Month 65.9 63.0 1.15 0.34

p=0.03

Vasopressor started, now what?

Restore perfusion to vital organs

Increasing MAP?

Bourgoin et al CCM 2005, 33, 780-786

Lactate

DO2

VO2

65 85

Increasing MAP?

Bourgoin et al CCM 2005, 33, 780-786

UOP

Creatinine

CrCl

65 85

Increasing MAP from 65 to 85 mmHg

•  Does not significantly improve: §  systemic oxygen metabolism (DO2/VO2) §  skin microcirculatory blood flow §  urine output , UF, CrCl, Cr §  splanchnic perfusion §  lactate clearance

LeDoux et al, Crit Care Med 2000 Bourgoin et al, Crit Care Med 2005

Clinical Application

•  Fluids or colloids (B) •  Dopamine or Norepinephrine first choice (C) •  Phenylephrine or Epinephrine second choice (D) •  Vasopressin for refractory shock (D) •  Dobutamine as inotrope (C)

•  Fluids or colloids (1B) •  Fluid challenge (1C) •  Dopamine or Norepinephrine first choice (1C) •  Epinephrine second choice (2B) •  Vasopressin in refractory shock (2C) •  Dobutamine as inotrope (1C)

2012 Guidelines

2012 Guidelines

How do I give it?

•  Is dopamine safer to give via PIV than norepinephrine?

– There is no evidence to suggest that – What evidence is there?

How do I give it?

•  My patients do not have central lines

How do I give it?

•  RCT •  PIV vs CVC •  Analyzed by ITT •  Results – less major complications with

CVC rather than PIV (0.64 vs 1.04, p<0.02)

•  The majority of complications in the PIV group were the inability to insert a PIV

What we want to know:

•  Were there extravasation injuries in the PIV group? –  Included very high doses

•  Up to 2 mg/hr (33.3 mcg/min) of norepinephrine or epinephrine

•  Up to 10 mg/kg/min of dopamine or dobutamine

– 19 patients in the PIV group had extravasation •  None of them required anything more than

observation and conservative treatment*

What does the study mean?

•  You can give pressors via PIV

•  There are risks with all pressors (including dopamine)

_________________________________

•  We need to investigate the use of pressors via IO

What if there is extravasation? •  If patient is relying on the pressor,

infuse via new access (IV, IO) •  Aspirate from the IV that infiltrated •  Give phentolamine (Regitine)

– Comes 5 mg / 1 mL – Place in 9 mL NS – Dose: 0.1 – 0.2 mg/kg (up to 10 mg) –  Inject a few mLs via the infiltrated catheter

and the remaining SQ around the borders of the extravasation

•  Consult plastic surgery

Push-Dose-Pressors

•  Term coined by Scott Weingart, MD

•  Used by OB anesthesia for a long time

•  Quick bolus of vasopressor during duress

Push-Dose-Pressors

•  Idea – Hypotension should be corrected quickly – Push drugs result in hypotension, so push

drugs should be used to correct hypotension

– Typically use phenylephrine or epinephrine – You might be able to use norepinephrine

(we need a study)

Push-Dose-Pressors EPINEPHRINE •  Receptors: Alpha and beta •  Mixing:

– 1 mL of epinephrine from cardiac epinephrine ampule (100 mcg/mL)

– 9 mL of normal saline in 10 mL syringe – 10 mL of epinephrine 10 mcg/mL (same

concentration as lidocaine with epi) •  Dose: 0.5 - 2 mL q 2-5 minutes

*** Do NOT give cardiac arrest dose (1 mg) to patients with a pulse

Push-Dose-Pressors PHENYLEPHRINE •  Receptors: Pure alpha

– No intrinsic inotropy – May cause increased coronary perfusion

which may increase CO –  I only use it in tachycardic patients

•  Mixing – 1 ml phenylephrine from vial (10 mg/mL) –  Inject into 100 mL bag normal saline – Phenylephrine 100 mcg/mL

•  Dose: 0.5 - 2 mL q 2 - 5 minutes

Push-Dose-Pressors

•  Pit-falls – Errors in mixing

•  Solution – Pre-mixed syringes

Conclusions

•  Fill the tank first •  The first line pressor choice should be

norepinephrine (Levophed) •  Pressors can be given via peripheral IV •  Need to evaluate pressors via IO •  Push-dose-pressors are coming to the

out-of-hospital setting

References •  EMCrit •  Berben JY, Bryant MF, Howard JM. Etiology and prevention of sloughs produced by L-norepinephrine (levophed). Annals of surgery, 1957. no. 6.

http://www.ncbi.nlm.nih.gov/pubmed/13488384. •  Bunker N, Higgins D. Peripheral administration of vasopressin for catecholamine-resistant hypotension complicated by skin necrosis. Critical care medicine,

2006. no. 3. http://www.ncbi.nlm.nih.gov/pubmed/16505698. •  Chen JL, O’Shea M. Extravasation injury associated with low-dose dopamine. The Annals of pharmacotherapy, 1998. no. 5.

http://www.ncbi.nlm.nih.gov/pubmed/9606475. •  Kahn JM, Kress JP, Hall JB. Skin necrosis after extravasation of low-dose vasopressin administered for septic shock. Critical care medicine, 2002. no. 8.

http://www.ncbi.nlm.nih.gov/pubmed/12163813. •  Khan JM, Mansoor S, Holmes JD. Reducing the morbidity from extravasation injuries. Annals of plastic surgery, 2002 no. 6.

http://www.ncbi.nlm.nih.gov/pubmed/12055433. •  Mcginn JT, Schluger J. Skin sloughs associated with levophed; pathogenesis, prevention and treatment. American journal of surgery, 1956 no. 4.

http://www.ncbi.nlm.nih.gov/pubmed/13362728. •  Pelner L, Waldman S, Rhoades MG. The problem of levarterenol (levophed) extravasation an experimental study. The American journal of the medical sciences,

1958no. 6. http://www.ncbi.nlm.nih.gov/pubmed/13606129. •  Raszka WV, Kueser TK, Smith FR, et al. The use of hyaluronidase in the treatment of intravenous extravasation injuries. Journal of perinatology : official journal of

the California Perinatal Association, 1999 no. 2. http://www.ncbi.nlm.nih.gov/pubmed/2358898. •  Ricard JD, Salomon L, Boyer A, et al. Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial. Critical care

medicine, 2013 no. 9. doi:10.1097/CCM.0b013e31828a42c5. http://www.ncbi.nlm.nih.gov/pubmed/23782969. •  Zucker G. Use of phentolamine to prevent necrosis due to levarterenol. Journal of the American Medical Association, 1957 no. 16 ( 20).

http://www.ncbi.nlm.nih.gov/pubmed/13415911. •  Zucker G, Eisinger RP, Floch MH, et al. Treatment of shock and prevention of ischemic necrosis with levarterenol-phentolamine mixtures. Circulation. 1960.

http://www.ncbi.nlm.nih.gov/pubmed/13788877. •  Ngan Kee WD, Khaw KS, Lau TK, et al. Randomised double-blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal

anaesthesia for non-elective Caesarean section. Anaesthesia. 2008 Dec;63(12):1319-26. doi: 10.1111/j.1365-2044.2008.05635.x. •  Mullner M, Urbanek B, Havel C, et al. Vasopressors for shock. Cochrane Database Syst Rev 2004;:CD003709. •  Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Task Force of the American College of Critical Care Medicine, Society of

Critical Care Medicine. Crit Care Med 1999;27:639. •  Moran JL, O’Fathartaigh MS, Peisach AR, et al. Epinephrine as an inotropic agent in septic shock: a dose-profile analysis. Crit Care Med 1993;21:70. •  Martin C, Papazian L, Perrin G, et al. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 1993;103:1826.

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1991;19:1395. •  Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care

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Care Med 1995;23:1962. •  De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362:779. •  Polito A, Parisini E, Ricci Z, et al. Vasopressin for treatment of vasodilatory shock: an ESICM systematic review and meta-analysis. Intensive Care Med

2012;38:9. •  Kahn JM, Kress JP, Hall JB. Skin necrosis after extravasation of low-dose vasopressin administered for septic shock. Crit Care Med 2002;30:1899. •  Marik PE, Mohedin M. The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA

1994;272:1354. •  Peters JI, Utset OM. Vasopressors in shock management: Choosing and using widely. J Crit Illness 1989;4:62. •  Havel C, Arrich J, Losert H, et al. Vasopressors for hypotensive shock. Cochrane Database Syst Rev 2011;:CD003709. •  Morelli A, Ertmer C, Rehberg S, et al. Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized,

controlled trial. Crit Care 2008;12:R143. •  Myburgh JA, Higgins A, Jovanovska A, et al. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 2008;34:2226. •  De Backer D, Aldecoa C, Njimi H, et al. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med 2012;40:725. •  Patel GP, Grahe JS, Sperry M, et al. Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock 2010;33:375. •  Mathur SM, Dhunna R, Chakraborty A. Comparison of dopamine and norepinephrine in the management of septic shock using impedance cardiography. Ind J

Crti Care Med 2007;11:186. •  Vasu TS, Cavallazzi R, Hirani A, et al. Norepinephrine or dopamine for septic shock: systematic review of randomized clinical trials. J Intensive Care Med

2012;27:172.

Acknowledgements

emcrit.org

Thank you!!!

Code3 Conference Planning Committee

Please let me know if you have any questions:

keepermanj@wusm.wustl.edu