Definition, etiology, pathogenesis, consequences Top
Shock is a life-threatening generalized form of acute circulatory failure associated with inadequate oxygen utilization by cells. In this state the circulation is unable to deliver enough oxygen to meet the demands of tissues. As a result, the patient develops cellular dysoxia that is associated with a transition to anaerobic metabolism and subsequent lactate production. Although it is frequently accompanied by hypotension (reduction of blood pressure), in the early stages of shock—referred to as compensated shock—blood pressure may be normal or even elevated.
Shock, as defined above, is due to one or more often a combination of the following pathophysiologic mechanisms.
1. A decrease in the total blood volume (absolute hypovolemia), referred to as hypovolemic shock, which may result from the following:
1) Loss of whole blood due to an internal or external hemorrhage. This leads to hemorrhagic shock.
2) A decrease in the plasma (effective circulating) volume due to the following causes:
a) Leakage of plasma to damaged tissues (trauma) or exudation from the skin surface (eg, burns, Lyell syndrome, Stevens-Johnson syndrome, exfoliative dermatitis).
b) Reduction of the extracellular fluid volume (dehydration) because of reduced water intake (most frequently in the elderly [with hypodipsia] or incapacitated persons) or an increased loss of water and electrolytes via the gastrointestinal (GI) tract (diarrhea and vomiting), kidneys (osmotic diuresis in diabetic ketoacidosis or hyperglycemic hyperosmolar state, polyuria and excessive excretion of sodium in glucocorticoid and mineralocorticoid deficiencies, or central or nephrogenic diabetes insipidus), or skin (fever, hyperthermia).
c) Shifting of fluids into the third space such as the intestinal lumen (ileus or intestinal obstruction) or less commonly to the serous cavities (such as the peritoneum; this may lead to ascites).
d) Increased vascular permeability in anaphylactic shock or septic shock.
2. Increased volume of the vascular bed, maldistribution of flow, or both, leading to relative hypovolemia with a potentially hyperkinetic state—distributive shock—due to vasodilation or peripheral shunting and a reduction in the effective tissue blood flow. The main etiologies of distributive shock:
1) Septic shock.
3) Neurogenic shock: Secondary to spinal cord injury, traumatic brain injury, stroke, brain edema, orthostatic hypotension (long-standing), or vasodilation caused by pain.
4) Hormone-induced shock: Secondary to acute adrenal insufficiency, thyroid storm, myxedema coma.
3. Cardiac dysfunction (usually secondary to acute myocardial dysfunction, arrhythmia, or valvular dysfunction) that causes decreased cardiac output due to loss of contractility or significant rhythm change. This leads to cardiogenic shock.
4. Impaired left ventricular filling due to compression of the heart secondary to cardiac tamponade, severely reduced venous return (eg, tension pneumothorax, abdominal compartment syndrome), intracardiac impairment of ventricular filling caused by heart tumors or intracardiac thrombi, or a sudden increase in cardiovascular resistance (pulmonary embolism, acute pulmonary hypertension in the course of acute respiratory failure). This leads to obstructive shock.
1. Compensatory responses by the body in an attempt to maintain homeostasis. Importantly, their effectiveness usually declines with time.
1) Compensatory autonomic response and adrenaline release from the adrenal glands, which causes tachycardia and attempts to maintain central perfusion (this leads to the constriction of precapillaries and veins in less essential organ vascular beds – first in the skin, then in muscles, and later in the visceral and renal circulation – and instead maintains perfusion to the vital organs such as the heart and the brain). In hypovolemic shock, the deficient plasma volume is replaced by transudation of intracellular fluid to the capillaries. In some cases of noncardiogenic shock, myocardial contractility (and sometimes also cardiac output) may increase. Hyperventilation and hyperglycemia can also occur as a result of increased sympathetic stimulation.
2) Stimulation of the renin-angiotensin-aldosterone system as well as secretion of antidiuretic hormone (ADH) and glucocorticoids, which all contribute to maintaining central perfusion and cause sodium and water retention.
3) Increased tissue oxygen uptake in response to low oxygen supply, which leads to increased deoxygenation of hemoglobin and decreased venous hemoglobin oxygen saturation (SvO2).
2. Metabolic and electrolyte disturbances due to hypoxia:
1) Increased anaerobic metabolism and lactate production, leading to metabolic acidosis (see Nonrespiratory Acidosis).
2) Release of potassium, phosphate, and some intracellular proteins (lactate dehydrogenase [LDH,], creatine kinase [CK], aspartate aminotransferase [AST], alanine aminotransferase [ALT]) to the extracellular fluid, increased sodium influx into the cells (due to impaired adenosine triphosphate synthesis). Both of these processes may lead to hyponatremia, hyperkalemia, and hyperphosphatemia.
3. Consequences of organ ischemia: Multiple organ dysfunction syndrome including acute kidney injury (prerenal azotemia), altered mental status (which may progress to coma), acute respiratory insufficiency (potentially leading to acute respiratory distress syndrome), acute liver failure, disseminated intravascular coagulation (DIC), GI bleeding (due to acute and erosive hemorrhagic gastropathy), gastric or duodenal stress ulcers, ischemic colitis, adynamic ileus, and penetration of microorganisms from the GI tract to the bloodstream.
Clinical features Top
1. Cardiovascular symptoms:
1) Tachycardia (in rare cases bradycardia may be observed, usually in the terminal phase before cardiac arrest).
2) Hypotension (traditionally defined as a drop in systolic blood pressure [SBP] <90 mm Hg or a significant decrease in SBP [eg, by >40 mm Hg], a drop in mean arterial pressure [MAP] [approximately a third of SBP plus two-thirds of diastolic blood pressure, DBP] <65-70 mm Hg [decreased DBP, and the resulting decreased MAP, may precede a drop in SBP]; the early phases of shock may be accompanied by orthostatic hypotension alone or no hypotension at all).
3) A low-amplitude and slow-rising pulse (at SBP <60 mm Hg the radial pulse is usually not palpable).
4) Reduced jugular vein filling (although this may be increased with comorbid cardiac tamponade, pulmonary embolism, or tension pneumothorax).
5) Chest pain.
6) Cardiac arrest (special attention is needed not to overlook pulseless electrical activity, which is undetected by electrocardiography [ECG] monitoring alone).
2. Symptoms of organ hypoperfusion:
1) Skin: Pale, mottled, and cold, sweating, or both (in septic shock the skin is usually dry and warm; in dehydration, dry and hypoelastic); delayed capillary refill (after releasing pressure on a nail plate or peripheral soft tissue, the pallor disappears only after >2 seconds); cyanosis.
2) Central nervous system: Anxiety, restlessness, confusion, psychomotor agitation, somnolence, stupor, coma, focal neurologic deficits.
3) Kidneys: Oliguria or anuria and other symptoms of acute kidney injury.
4) Muscles: Weakness.
5) GI tract: Nausea, vomiting, flatulence, weak or no peristaltic sounds, bleeding.
6) Liver: Jaundice (a rare symptom, which may occur late or after the patient’s recovery from shock).
7) Respiratory system: Variable breathing patterns are possible. Initially, breaths may be shallow and rapid (in metabolic acidosis respiration may be slower but deeper, or even fast and deep – the Kussmaul respirations); subsequently, the respiratory rate may decrease and the patient can develop apnea. Acute respiratory failure with hypoxia (type I), inappropriate hypercapnia (type II), or both may occur.
3. Symptoms and signs of the underlying condition: Dehydration, bleeding, anaphylaxis, infection (sepsis), cardiovascular diseases, pulmonary embolism, tension pneumothorax, ileus, and other conditions.
The classically described triad of shock (hypotension, tachycardia, oliguria) may not be present together in all cases.
The clinical diagnosis of shock based on signs, symptoms, and results of biochemical tests is usually straightforward, but establishing the cause of shock may be more difficult; sometimes this is possible on the basis of history (eg, fluid or blood loss, symptoms of infection or anaphylaxis) or physical examination (eg, signs of bleeding, dehydration, cardiac tamponade, or tension pneumothorax). When evaluating the possible etiologies of shock, it is also important to consider other causes of reduced oxygen supply and tissue hypoxia (anemia, respiratory insufficiency, poisonings with substances that inhibit blood oxygen transport and cellular oxygen utilization).
1. Cardiovascular investigations:
1) Blood pressure measurements (including the use of invasive methods such as arterial cannulation).
2) 12-lead ECG and continuous ECG monitoring looking for signs of arrhythmias, myocardial ischemia or infarction, or other heart diseases.
3) Echocardiography may be helpful in determining the cause of cardiogenic or obstructive shock (myocardial dysfunction, valvular dysfunction, cardiac tamponade; focused ultrasound allows for the assessment of left ventricular pressures and volumes through direct and indirect measures). When hemodynamic assessment is needed, echocardiography may be preferable, given its noninvasive approach.
4) Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP): Measurements of CO and PCWP are sometimes performed in the case of diagnostic uncertainties and treatment difficulties. Measurements of PCWP using a Swan-Ganz (pulmonary artery) catheter may be useful in the assessment of volume status and preload (LV filling), which is essential for the differential diagnosis and ultimately for the therapeutic plan. PCWP reflects the left atrial pressures and is an indirect indicator of the LV end-systolic pressure; PCWP values of ~15 to 18 mm Hg indicate optimal LV filling. The Swan-Ganz catheter allows for the measurement of CO using the thermodilution method (other methods of CO measurements are also available). CO is reduced in cardiogenic and obstructive shock, and usually increased in the initial phases of hypovolemic shock as well as in septic or anaphylactic shock. Of note, the evidence for efficacy of any invasive cardiac output-measuring devices in terms of improving patient-important outcomes is lacking and therefore the use of Swan-Ganz catheters is usually reserved for complex patients who are not otherwise responding to initial therapy.
5) Dynamic measures of volume status: Measures of volume status such as pulse pressure variation (PPV), systolic pressure variation (SPV), stroke volume variation (SVV), passive leg raise, and inferior vena cava (IVC) collapsibility attempt to predict fluid responsiveness of patients with shock in order to guide fluid resuscitation. PPV, SPV, SVV, as well as IVC collapsibility reflect changes in hemodynamic measurements that accompany respiration-related fluctuations in the intrathoracic pressure. Patients who are volume-responsive tend to have larger degrees of variation in hemodynamic measures during the respiratory cycle. These measurements have not gained widespread acceptance, possibly due to limitations such as lack of applicability; they are only useful in patients receiving full mechanical ventilation (no spontaneous breathing activity) and with no arrhythmias. Another limitation is that the sensitivity of the test is affected when tidal volumes <8 mL/kg of ideal body weight are used.
2. Laboratory tests of the venous blood:
1) Serum biochemical tests:
a) Assessment of the effects of shock: Elevated levels of lactate, electrolyte disturbances (sodium and potassium levels); elevated levels of creatinine, urea/blood urea nitrogen, bilirubin, and glucose; elevated AST, ALT, CK, or LDH levels. We recommend measuring serum lactate levels in all patients suspected of shock and using the trend in lactate to guide, monitor, and assess the ongoing management of shock.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to indirectness, as mostly studied in patients with septic shock. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. doi: 10.1001/jama.2010.158. PubMed PMID: 20179283; PubMed Central PMCID: PMC2918907. Zhang Z, Xu X. Lactate clearance is a useful biomarker for the prediction of all-cause mortality in critically ill patients: a systematic review and meta-analysis*. Crit Care Med. 2014 Sep;42(9):2118-25. doi: 10.1097/CCM.0000000000000405. Review. PubMed PMID: 24797375.
b) Elevated levels of cardiac troponins, CK-MB, or myoglobin may indicate acute myocardial infarction (MI).
c) Elevated levels of natriuretic peptides (B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide) may indicate heart failure being either a cause or a consequence of shock.
2) Complete blood count:
a) Hematocrit, hemoglobin concentration, and red blood cell count: These are reduced in hemorrhagic shock (except for the initial phase) and usually increased in other forms of hypovolemic shock.
b) White blood cell count: Neutrophilic leukocytosis or leukopenia in septic shock. Leukocytosis and increase in neutrophil counts may also be observed in other forms of shock (eg, hypovolemic). Eosinophilia may be present in some cases of anaphylaxis.
c) Platelet count: Thrombocytopenia is usually the first sign of DIC (most frequently developing in septic shock or after a major trauma), but it may also be a result of massive bleeding and packed red blood cells transfusions.
3) Coagulation tests: Prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) as well as low fibrinogen levels may suggest DIC or result from posthemorrhagic or posttransfusion coagulopathy; sometimes prolonged PT and prolonged aPTT are the manifestations of liver failure (either acute or chronic). Elevated D-dimer levels are not specific to pulmonary embolism, as they may also occur in DIC and other conditions.
3. Pulse oximetry: Monitor for a possible fall in SaO2.
4. Arterial blood gases: Nonrespiratory or mixed acidosis. Respiratory alkalosis may sometimes be present in the early stages of shock due to hyperventilation; possible hypoxemia (see Acid-Base Disturbances).
5. Imaging studies: Chest radiographs: Look for the signs of heart failure (cardiac enlargement, pulmonary congestion, pulmonary edema) and causes of respiratory insufficiency or sepsis. Chest computed tomography (CT) scans are indicated in patients with suspected pulmonary embolism (computed tomography angiography [CTA]), aortic dissection, or aortic aneurysm rupture. Plain abdominal radiographs are performed in the case of suspected GI perforation or mechanical intestinal obstruction. Abdominal ultrasonography or CT is used to search for the source of infection in sepsis. Venous ultrasonography and pulmonary CTA (pulmonary embolism protocol) is indicated in the case of suspected deep vein thrombosis or pulmonary embolism. Head CT scans are indicated in the case of suspected stroke, brain edema, or posttraumatic lesions.
6. Blood group is to be determined in each patient either directly or on the basis of medical records.
7. Other studies: Venous blood hemoglobin oxygen saturation (preferably in the superior vena cava [SvcO2] or pulmonary trunk [mixed venous blood – SvmO2]) and venous blood gases from those central areas (SvcO2 <70% or SvmO2 <65% indicates compromised oxygen delivery to the tissues and a compensatory increase in oxygen extraction from the blood), microbiology (in septic shock), hormonal tests (thyroid-stimulating hormone and free thyroxine in the case of suspected myxedema coma or thyroid storm, cortisol in the case of suspected adrenal crisis), toxicology (suspected poisoning), allergy tests (IgE and allergic skin tests after recovery from anaphylactic shock).
1. Maintain the airway (see Cardiac Arrest and Head Injury), intubate the patient, and start mechanical ventilation as deemed necessary. Note that introducing positive pressure ventilation in addition to patient sedation and effects of the drugs used during intubation may all lead to hypotension. Be prepared to take appropriate action to treat worsening hypotension, if needed (rapid volume replacement, vasoconstrictors).
2. Position the patient with elevated lower extremities (Trendelenburg position). This may be transiently helpful in hypovolemic hypotension, particularly when no medical equipment is available, but it may impair ventilation as well as cardiac function in patients with cardiogenic shock and pulmonary congestion.
3. Insert intravascular catheters:
1) Two large-bore catheters in peripheral veins (preferably ≥1.8 mm [≤16 gauge]) to allow for effective fluid resuscitation (see below).
2) Central venous catheter in patients in whom administration of multiple drugs (including catecholamines; see below) is necessary. This also allows for the monitoring of central venous pressure (CVP), although recent evidence suggests a lack of benefit in the mandatory use of CVP to target fluid resuscitation in shock. We suggest that central venous catheter insertion and CVP monitoring is not essential in all shock patients.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to imprecision. ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. doi: 10.1056/NEJMoa1404380. Epub 2014 Oct 1. PubMed PMID: 25272316. ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. doi: 10.1056/NEJMoa1401602. Epub 2014 Mar 18. PubMed PMID: 24635773; PubMed Central PMCID: PMC4101700. Marik PE, Cavallazzi R. Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense. Crit Care Med. 2013 Jul;41(7):1774-81. doi: 10.1097/CCM.0b013e31828a25fd. PubMed PMID: 23774337.
3) Arterial catheter (usually in the radial artery) to allow for invasive blood pressure monitoring (not essential in shock easily responding to therapy). Central venous and arterial line placement should not delay appropriate treatment.
4. Treat the causes of shock (see below) while maintaining cardiovascular function and tissue oxygen supply.
1) Discontinue all antihypertensive drugs that may have been used by the patient.
2) In most types of shock intravenous fluid resuscitation is essential; an exception is cardiogenic shock with signs of pulmonary congestion. In theory, colloids restore the intravascular volume by remaining almost entirely in the circulation (plasma substitutes, eg, gelatin, 4%-5% albumin solution) or by remaining in the blood vessels and causing transfer of water from the extravascular to the intravascular space (plasma volume expanders: hydroxyethyl starch [HES], 20% albumin solution, dextrans); crystalloid solutions compensate for the deficit of the entire extracellular fluid (both extravascular and intravascular). Glucose (dextrose) solutions increase the total body water (both extracellular and intracellular fluid). It has not been conclusively proven that colloid solutions (6% or 10% HES, 4% gelatin, dextran, albumin) reduce mortality in comparison to crystalloid solutions (Ringer solution or 0.9% NaCl) and available evidence suggests harmful effects of starches, especially in septic shock. The 2013 National Institute for Health and Care Excellence guidelines recommend to start fluid resuscitation using crystalloids containing 130 to 154 mmol/L of sodium, with a bolus of 500 mL administered over <15 minutes. Usually, the initial management involves the administration of 1000 mL of a crystalloid (or 300-500 mL of a colloid) over 30 minutes, and then the infusion is repeated, depending on the effects on blood pressure, CVP, urine output, or other dynamic measures of volume status, as well as adverse effects (symptoms of volume overload). Balanced crystalloids, that is, crystalloids with an electrolyte content (specifically chloride) closer to that of plasma, may be preferred. In the case of intensive fluid resuscitation, we suggest to avoid the use of 0.9% NaCl alone,Evidence 3Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirect comparisons and imprecision. Rochwerg B, Alhazzani W, Sindi A, et al; Fluids in Sepsis and Septic Shock Group. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med. 2014 Sep 2;161(5):347-55. doi: 10.7326/M14-0178. Review. PubMed PMID: 25047428. because administration of large volumes of this solution (sometimes incorrectly called normal [physiologic] saline) causes hyperchloremic acidosis, hypernatremia, and hyperosmolarity. Do not use hypotonic fluids (for example, 5% glucose) for fluid resuscitation in shock even in patients with hypernatremia, as this fluid will not remain in the intravascular space.
3) In the case of persistent hypotension despite fluid resuscitation, a continuous IV infusion of catecholamines should be started (optimally via a central venous catheter). For most etiologies of shock, we recommend starting with norepinephrine, usually 1 to 20 microg/min (up to 1-2 microg/kg/min).Evidence 4Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of intervention). 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 Mar;40(3):725-30. doi: 10.1097/CCM.0b013e31823778ee. PubMed PMID: 22036860. Levy B, Perez P, Perny J, Thivilier C, Gerard A. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study. Crit Care Med. 2011 Mar;39(3):450-5. doi: 10.1097/CCM.0b013e3181ffe0eb. PubMed PMID: 21037469. De Backer D, Biston P, Devriendt J, et al; SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010 Mar 4;362(9):779-89. doi: 10.1056/NEJMoa0907118. PubMed PMID: 20200382. However, epinephrine 0.05 to 0.5 microg/kg/min or dopamine (this is currently discouraged in septic shock) 3 to 30 microg/kg/min may be considered. In anaphylactic shock, start with an intramuscular injection of 0.3 to 0.5 mg epinephrine to the lateral thigh.
4) In patients with evidence of low CO despite adequate hydration (or volume overload), dobutamine in a continuous IV infusion (2-20 microg/kg/min) may be beneficial (this requires careful consideration in the presence of arrhythmias, including sinus tachycardia, as dobutamine may worsen the arrhythmia). In the case of concomitant hypotension, you may simultaneously administer vasoconstrictors.
5) At the same time administer oxygen therapy (see Oxygen Therapy; maintaining a high oxygen saturation increases the oxygen supply to tissues; SaO2 <95% is an indication for oxygen therapy).
6) In patients with signs of hypoperfusion and hematocrit <30% despite the above treatment, consider transfusion of packed red blood cells (see Blood and Blood Product Transfusion).
5. The basis of management in patients with lactic acidosis is treatment of the underlying condition and maintaining cardiovascular function. Consider IV administration of NaHCO3 in patients with a pH <7.15 (7.20) and bicarbonate levels <14 mmol/L, although beneficial effects of this intervention have not been proven.
6. Monitor vital parameters (blood pressure [initially in most circumstances target MAP is ≥65 mm Hg; exceptions: see Hemorrhagic Shock], pulse rate, respiratory rate), level of consciousness, ECG, SaO2, blood lactate levels (aim to normalize), blood gases, sodium and potassium levels, renal and liver function tests, CVP, as well as CO, PCWP, or dynamic measures of volume status, when necessary.
7. Protect the patient from hypothermia and ensure a quiet environment.
8. In the case of persistent shock and the need for an ongoing intensive care unit–level care:
1) Prevent GI bleeding and thromboembolic complications (do not use anticoagulants in patients with active bleeding or at high risk of bleeding; in such cases use mechanical methods only): see Primary Prevention of Venous Thromboembolism.
2) Treat hyperglycemia (in patients with glucose levels >10-11.1 mmol/L [180-200 mg/dL]), possibly with a continuous IV infusion of a short-acting insulin, but avoid hypoglycemia. Make attempts to maintain blood glucose levels from between 6.7 and 7.8 mmol/L (120-140 mg/dL) to between 10 and 11.1 mmol/L (180-200 mg/dL).