Management of Perioperative Vasoplegia

Educational Objectives

The goal of this program is to improve management of vasoplegia. After hearing and assimilating this program, the clinician will be better able to:

1. Cite diagnostic criteria in vasoplegia.

Summary

Vasoplegia or vessel paralysis: is broadly defined as excess vascular smooth muscle relaxation; it is seen in distributive shock states, eg, septic shock, but vasodilatory shock can coexist with cardiogenic, neurogenic, and anaphylactic shock; general diagnostic criteria — mean arterial pressure (MAP) <65 mm Hg, 0.2 to 0.5 μg/kg per min norepinephrine dosing, systemic vascular resistance (SVR) <800 dynes/sec/cm⁻⁵, cardiac index >2.2 L/min/m², and nonresponsiveness to fluid boluses; 20% of patients undergoing procedures on cardiopulmonary bypass (CPB) have vasoplegia; there is not much data on frequency of vasoplegia in noncardiac surgeries; many of the diagnostic criteria can be applied to patients in general surgeries

Molecular pathophysiology: vascular hyperresponsiveness to vasopressors has 3 main components, which are central, cellular, and intracellular; vasoplegia occurs due to inflammatory cytokine release and dysregulation of catecholamine receptors; there is a miscommunication in neuroimmune pathways leading to excessive nitric oxide release; desensitization of receptor pathways and less production of catecholamines occurs; alteration of secondary pathways involves overproduction of nitric oxide synthetase, causing vasodilatation; vasoplegia is associated with increased mortality, worsened neurologic and cardiogenic outcomes, risk for kidney injury, longer duration of hospital stays and mechanical ventilation, and higher rates of infection; local vascular autoregulation maintains adequate tissue perfusion at organ level, but it has been shown that MAP <65 mm Hg during CPB increases risk for end-organ injury

Risk factors: include left ventricular ejection fraction <40%, male sex, older individuals, obesity, presence of left ventricular assist device, use of CPB as it directly activates inflammatory cascade causing hemodilution, longer CPB times, hypotension on initiation of CPB, perioperative angiotensin-converting enzyme inhibitor use, and infective endocarditis

Vasoplegia treatment pathway: involves confirming a diagnosis of vasoplegia; ruling out mechanical or equipment concerns; correction of physiologic factors; conventional vasopressors and off-label medicines can be used; CPB parameters (vascular and nonvascular components) should be optimized; recent Cochrane analysis concluded there is not sufficient evidence to conclude that one vasopressor is better than another; it is up to the treating physician to choose the vasopressor

Causes of hypotension: include arterial line malfunctioning leading to measurement errors, new ventricular dysfunction or arrhythmias, hypovolemic shock, anaphylaxis, aortic dissection, mechanical failure of CPB circuit, wrong aorta cannula size, malpositioning of cannula, medication errors, unintentional torsion or clamping of aorta cannula, and inappropriate anesthetic doses

Optimizing CPB parameters: vascular components include vessel length and diameter, number of vessels, and precapillary shunting; nonvascular components include bypass flow rates, blood temperature, hematocrit, and blood viscosity; other controllable bypass parameters include pump blood flow based on aorta cannula size; pumping excessive blood through a small cannula leads to hematuria and hemolysis; blood viscosity follows Poiseuille law; intravascular tubing size and blood flow are important variables; viscosity is directly proportional to SVR; overdilution of the patient results in vasoplegia

Vasopressors: norepinephrine — increases MAP and cardiac index without increasing heart rate; it is potent and does not act on beta-2 receptors; disadvantages include increased oxidative stress and interaction with cellular energy metabolism; vasopressin — is deficient in septic shock; terlipressin is a long-acting vasopressin analogue, that has predominantly vasopressin 1 receptor activity, with some advantages but it is not approved in the United States; vasopressin is more expensive vs norepinephrine

Off-label medications: methylene blue — it has been used to treat vasoplegia for 20 yr, but has not received Food and Drug Administration (FDA) approval; it has been approved to treat methemoglobinemia; it counteracts endothelial nitric oxide activity, scavenges nitric oxide directly, inhibits cyclic guanosine monophosphate activity, and attenuates ischemia reperfusion injury; it is used in septic shock, in patients after cardiac surgery, drug poisoning, eg, cyanide toxicity, anaphylactic shock, and postreperfusion syndrome in liver transplantations; hydroxocobalamin — is FDA approved for cyanide toxicity; an off-label used to treat vasoplegia; it is the highly bioavailable form of vitamin B12 (cyanocobalamin); it inhibits nitric oxide synthetase (similar to methylene blue)

Nonvasopressors: glucocorticoids inhibit nitric oxide and increase adrenergic receptor expression; threshold to give steroids should be extremely low

Future directions: angiotensin II is approved by FDA; selepressin, vitamin C, hydrocortisone-ascorbic acid-thiamine therapy, and prostaglandin inhibitors are on the horizon but have not yet received approval

Readings

Barnes TJ, Hockstein MA, Jabaley CS. Vasoplegia after cardiopulmonary bypass: a narrative review of pathophysiology and emerging targeted therapies. SAGE Open Med. 2020; 8:2050312120935466; doi: 10.1177/2050312120935466; El-Kadi G, Magdy H, Abdelnaeem K, et al. Terlipressin in norepinephrine-resistant hyperdynamic shock after cardiac surgery. Res Opin Anesth Intensive Care. 2021; 8:147; doi: 10.4103/roaic.roaic_12_21; Habib AM, Elsherbeny AG, Almehizia RA. Methylene blue for vasoplegic syndrome postcardiac surgery. Indian J Crit Care Med 2018; 22:168-73; doi: 10.4103/ijccm.IJCCM_494_17; Levin MA, Lin HM, Castillo JG, et al. Early on-cardiopulmonary bypass hypotension and other factors associated with vasoplegic syndrome. Circulation. 2009; 120:1664-1671; doi: 10.1161/CIRCULATIONAHA.108.814533; Levy B, Fritz C, Tahon E, et al. Vasoplegia treatments: the past, the present, and the future. Crit Care. 2018; 22:52; doi: 10.1186/s13054-018-1967-3; Ortoleva JP, Cobey FC. A systematic approach to the treatment of vasoplegia based on recent advances in pharmacotherapy. J Cardiothorac Vasc Anesth. 2019; 33:1310-1314; doi: 10.1053/j.jvca.2018.11.025; Saha BK, Burns SL. The story of nitric oxide, sepsis and methylene blue: a comprehensive pathophysiologic review. Am J Med Sci. 2020; 360:329-337; doi: 10.1016/j.amjms.2020.06.007; Shaefi S, Mittel A, Klick J, et al. Vasoplegia after cardiovascular procedures-pathophysiology and targeted therapy. J Cardiothorac Vasc Anesth. 2018; 32:1013-1022; doi: 10.1053/j.jvca.2017.10.032; Shah PR, Reynolds PS, Pal N, et al. Hydroxocobalamin for the treatment of cardiac surgery-associated vasoplegia: a case series. L'hydroxocobalamine pour le traitement de la vasoplégie associée à la chirurgie cardiaque: une série de cas. Can J Anaesth. 2018; 65:560-568; doi: 10.1007/s12630-017-1029-3.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. In his lecture, Dr. Kothari presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Kothari was recorded at the 69th Annual Convention and Conclave of the American Osteopathic College of Anesthesiologists, held September 25-28, 2021, in Palm Beach, FL, and presented by the American Osteopathic College of Anesthesiologists. For information on future CME activities from this presenter, please visit aocaonline.org. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

AN641403

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.