Management of Refractory Shock

Introduction:

The shock occurs when the tissues' supply of oxygen and nutrients is insufficient given their needs. It is caused by the circulatory system's inability to adequately meet the tissues' blood needs for metabolism and the insufficient elimination of metabolic waste products. Hypovolemic shock is the most frequent cause in children, whereas septic shock is the most frequent cause in adults.

What Is Refractory Shock?

Refractory shock is a possible life-threatening form of circulatory failure featuring inadequate tissue perfusion (reduced tissue transport of nutrients and oxygen), hypotension (low blood pressure), and failure of organs in reaction to vasopressors (drugs that narrow (constrict) blood arteries, raising blood pressure). Refractory shock must be managed by addressing the root cause and recovering organ perfusion with resuscitation of fluids and vasopressors.

What Is the Epidemiology of Refractory Shock?

Refractory vasodilatory shock occurs when there is a circulatory failure. It usually comes after septic shock. More than 50 % of people die from refractory shock. Approximately six to seven percent of critically ill ICU patients could experience refractory shock.

What Are the Clinical Manifestations of Refractory Shock?

The symptoms of refractory shock include end-organ dysfunction. Assessing the degree of organ dysfunction should be the primary goal of the physical examination. The cardiovascular system exhibits low blood pressure and pump failure, the gastrointestinal tract exhibits ileus (obstruction of the ileum or another section of the intestine that causes severe pain) or ischemia (poor blood supply), the respiratory system exhibits hyperventilation (rapid or deep breathing) or acute respiratory distress syndrome (ARDS). It is a severe lung disease that lowers blood oxygen levels, and the skin exhibits decreased capillary refill. The central nervous system exhibits altered sensations.

Dyspnea (shortness of breath), capillary refill, mental status, and urine output are subjective indicators of oxygen delivery. In contrast, objective indicators include lactate level, mixed venous saturation, heart rate, and blood pressure.

How to Diagnose Refractory Shock?

• The primary goal of the examination should be to identify the original reason and any secondary causes that are treatable, such as hypovolemia (a reduction in the amount of blood that is circulated throughout the body), pump failure (the heart's failure to supply the body with enough oxygenated blood to meet its metabolic needs), or blockage that is producing shock.

• Patients need to be under constant cardiopulmonary surveillance.

• The following laboratory tests should be kept an eye on:

  • Complete blood count with differential (CBC-d).

  • A fundamental metabolic profile with a test for liver function.

  • Disseminated intravascular coagulation (DIC) panel.

  • Arterial blood gas.

  • Urinalysis.

  • If intubated, pan cultures (blood, urine, wound, and tracheal).

• Monitoring of inflammatory markers, such as lactate levels and C-reactive protein or procalcitonin levels, is necessary.

• The severity of ARDS should be monitored with a chest X-ray.

How to Manage Refractory Shock?

The contributory etiology must be located and treated as the first step in care. Early diagnosis and treatment of compensated shock can stop it from developing into refractory shock. In cases of hypovolemic shock, fluid resuscitation should be given, while in cases of fluid-refractory shock should be used. Some of the possible ways to manage refractory shock are as follows:

• Reduce Sedation: Through systemic vasodilation and myocardial depression, sedatives aggravate hypotension. The Surviving Sepsis guidelines advise reducing sedation in sepsis patients reliant on mechanical breathing.
• Glucocorticoid Therapy: Vasodilation brought on by inflammation is lessened by glucocorticoids. Refractory vasodilation may result from relative adrenal insufficiency in those suffering from shock. About 50 or 100 milligrams of hydrocortisone can be used every six or eight hours. Combining vasopressin has been shown to have a synergistic impact. Although hydrocortisone infusion has demonstrated enhanced shock reversal, its impact on shock duration, intensive care unit (ICU) stay, and mortality is still debatable.
• Acidemia Correction: When arterial pH is below 7.15, there is a significant reduction in the reactivity of vasopressors in acidic settings due to decreased catecholamine signaling. Although sodium bicarbonate can treat metabolic acidosis, it has adverse side effects, including hypernatremia, respiratory acidosis, paradoxical intracellular acidosis, hypocalcemia, and high lactate levels. A synthetic non-bicarbonate buffer that can replace sodium bicarbonate is tris hydroxymethyl-aminomethane (tromethamine). However, there needs to be more data on its effectiveness and safety. Alkali treatment is, at most, a temporary solution and necessitates administering a large volume of intravenous (IV) fluid.
• Renal Replacement Therapy: Acute renal injury linked to severe shock may restrict acidemia's clearance ability. Continuous renal replacement treatment can enhance vasopressor response and rectify metabolic abnormalities in some patients with acute kidney damage. In individuals suffering from septic shock with severe acute kidney damage, a shorter time between the start of vasopressors and continuous renal replacement therapy could be related to better results.
• Calcium Augmentation: Patients with severe sepsis frequently experience hypocalcemia, which may be caused by calcium chelation by citrate in transfused blood products, acquired parathyroid insufficiency, vitamin D inadequacy, renal 1a-hydroxylase insufficiency, or acquired calcitriol resistance. Intracellular calcium signaling is a crucial mechanism that causes the contraction of cardiac and vascular smooth muscle contraction. As a result of impaired circulatory function, severe hypocalcemia can result in hypotension. By boosting vascular tone after calcium chloride is given as a bolus, mean arterial pressure (MAP) is increased without raising cardiac output. Hypercalcemia and a blunting of beta-adrenergic actions are potential side effects.
• Vitamin C: An essential component needed for synthesizing naturally occurring norepinephrine and vasopressin is vitamin C (ascorbic acid). The body cannot produce vitamin C. Thus, it must be taken as a supplement. Patients who are critically ill often have a relative or absolute vitamin C shortage, which can lead to refractory shock from a lack of endogenous catecholamines. Vitamin C enhances macrophage and T-cell immunity and has potent antioxidant effects. High-dose vitamin C administered intravenously may lessen inflammation, improve hemodynamic parameters, and improve organ function.
• Thiamine: Thiamine, a form of vitamin B1, is a crucial component in the metabolism of lactate and oxidative energy. Patients in septic shock often have a relative or absolute thiamine shortage, which can worsen their cardiovascular health and cause lactic acidosis. The need for CRRT may be lessened by IV thiamine supplementation, better lactate clearance, and renal function. Thiamine has been demonstrated to improve shock reversal and lessen the degree of organ failure when taken with hydrocortisone and a high dosage of vitamin C.
• ECMO: Patients with post-cardiotomy shock benefit from temporary good cardiopulmonary support from extracorporeal membrane oxygenation (ECMO). It enhances the delivery of oxygen systemically and aids in treating refractory hypoxemia brought on by pulmonary failure. By removing carbon dioxide and managing acid-base balance, it gets better. It is utilized in refractory cardiogenic shock and enhances myocardial function.
• TPE: In refractory septic shock, a breakthrough technique called therapeutic plasma exchange (TPE) can restore protective substances in the plasma while simultaneously removing pathologically elevated cytokines.

Future Treatments:

• Terlipressin is a lengthy-acting vasopressin equivalent that only partially selectively works on the V1a receptor. Like vasopressin, it raises MAP and lowers the need for vasopressors during vasodilatory shock. However, when given as a bolus, it may result in a drop in cardiac output, necessitating the administration of inotropes.

• A synthetic selective vasopressin-V1a receptor agonist, selepressin. Like vasopressin, it raises MAP and lowers the need for catecholamines. Still, it does not affect thrombosis brought on by the release of Von Willebrand factor or fluid overload from retaining water.

• Angiotensin II, a synthetic version of human angiotensin II, is a crucial part of the renin-angiotensin-aldosterone system. Sepsis may manifest as a functional angiotensin II or angiotensin-converting enzyme (ACE) insufficiency, resulting in refractory shock. Angiotensin II improves outcomes in patients with less severe shock, raises MAP, and reduces the requirement for additional vasopressors.

Conclusion:

Refractory shock can be fatal, with a death rate of up to 60 %. Identifying the underlying cause, timely treatment, and early induction of combination vasopressor medication are essential to survival. Unfortunately, multi-organ failure happens frequently, even with several rescue medications, making patient monitoring essential. When determining drug interactions and selecting a rescue therapy, an interprofessional team composed of intensivists, nurses in intensive care units, and physicians should collaborate.