Hypovolemic Shock Pathophysiology, Symptoms, Signs, Treatment

What Is Hypovolemic Shock: Definition

Hypovolemic shock is an urgent medical condition, which occurs when a rapid decrease of the volume of the intravascular fluid–usually due to severe bleeding–results in inadequate perfusion of the peripheral tissues and, eventually, in multiple organ failure ^1,43.

Hemorrhagic shock is hypovolemic shock caused by bleeding.

Typical symptoms and signs: a person “does not look right,” is anxious, has pale, cool and sweaty skin and weak pulse, is lethargic and may lose consciousness.

Treatment includes stopping bleeding, intravenous fluid infusion, oxygen and drugs.

Table 1. Hypovolemic shock at a glance:
vital signs and first aid

Causes and Risk Factors

The most common cause of hypovolemic shock in adults is severe bleeding, and in children diarrhea ¹.

Causes of hypovolemia:

Loss of blood ¹
- External bleeding: penetrating injury, heavy menstruation, scalp tear ¹
- Gastrointestinal or rectal bleeding (blood in the stool):
  - Rupture of the esophageal varices (in chronic alcohol abuse with liver cirrhosis)
  - Esophageal tear due to violent vomiting, mostly in alcoholics (Mallory-Weiss syndrome)
  - Rupture of hemorrhoids
  - Aorto-intestinal fistula ¹
  - Bleeding peptic (gastric or duodenal) ulcer or gastric perforation (stomach cancer) or Meckel’s diverticulum ^1,23
  - Ulcerative colitis
  - Ischemic colitis
  - Intestinal perforation (for example, in diverticulitis)
  - Iron toxicity ⁵
  - Colorectal cancer (after age of 50)
  - Bleeding disorders, such as hemophilia ²³
- Other causes of internal bleeding:
  - Spleen rupture in car/motorbike accidents ¹
  - Rupture of the aortic aneurysm or aortic dissection ¹
  - Rupture of hepatic hemangioma ¹⁹
  - Retroperitoneal bleeding (anticoagulant therapy with warfarin or heparin in individuals with deep venous thrombosis) ³
  - Fracture of the pelvis or femur ¹
  - Hemorrhagic pancreatitis
  - Minor injuries in hemophilia
  - Bleeding during or after surgery
- Pregnancy-related bleeding:
  - Ruptured ectopic pregnancy ¹
  - Placenta previa ¹
  - Placental detachment (abruptio placentae) ¹
  - Uterine rupture ³
  - Bleeding after delivery ²
Blood donation
Loss of blood plasma
- Severe burns affecting >15% skin surface ^2,23
Decreased water intake ²³
Water loss
- Excessive sweating
- Repeated vomiting
- Severe diarrhea: gastroenteritis caused by rotavirus in small children (stomach flu), cholera ^2,3
- Excessive urination or polyuria:
  - Diabetes mellitus ¹⁵, diabetic ketoacidosis ²³
  - Diabetes insipidus
  - Diuretics
  - Salt-wasting kidney diseases (polycystic kidney disease) ¹⁵
  - Hypercalcemia ²¹
Endocrine causes:
- Severe, acute thyrotoxicosis (“thyroid storm”) with high fever, excessive sweating and diarrhea ³⁶
- Acute adrenal insufficiency (“adrenal crisis”) in acute Addison’s disease with polyuria, vomiting and diarrhea ⁴²
Second spacing: The fluid moves from the blood into the “second space” (the space between the cells, which is also called extracellular or interstitial space) and causes edema:
- Hyponatremia (a decrease in osmotic pressure of the blood results in a shift of water from the blood into the body cells)
- Congestive heart failure (blood pooling in the venous system and consequent escape of water into the interstitial tissue [edema] and a decrease of the blood volume in the arteries (arterial hypovolemia) ¹¹
- In anaphylactic and septic shock, the permeability of the blood vessels increases, so some fluid escapes from the blood into the interstitial space ¹⁸
Third spacing: Fluid accumulation in the body spaces where normally is no or only little fluid (the abdominal cavity, retroperitoneal space, lungs, pleural space, pericardial sac):
- Aortic dissection (blood pooling in the newly formed space in the aortic wall)
- Burns — fluid accumulation in the skin blisters ¹⁸
- Soft tissue trauma
- Pancreatitis — pancreatic enzymes and cytokines damage the blood vessels what results in the escape of fluid from the blood ¹⁵
- Peritonitis ¹⁵
- Pulmonary edema
- Pleural effusion ¹⁵
- Intestinal obstruction, paralytic ileus, volvulus ³
- A decrease of oncotic pressure of the blood plasma due to low blood protein levels and hypoalbuminemia can result in the escape of fluid from the blood into the body tissues and cavities:
  - Kidney disease with nephrotic syndrome with anasarca [generalized edema]¹²
  - Protein malnutrition [Kwashiorkor] can result in distended bellies in starving children ¹²
  - Liver cirrhosis resulting in ascites — accumulation of the fluid in the abdominal cavity ¹³
  - Protein losing enteropathy ²³
- Ovarian hyperstimulation syndrome ²⁰
- Sickle cell anemia with splenic sequestration, mostly in young children ²⁸
Systemic capillary leak syndrome ²⁴

NOTE: Many authors use the term third spacing for both second as third spacing.

Differential Diagnosis

There are other types of shock and other conditions that may resemble hypovolemic shock:

Distributive shock due to massive vasodilation with an increase in the volume of the intravascular space with insufficient volume of the existing blood to fill this space and therefore a drop of blood pressure
- Septic shock due to infection ⁷
- Toxic shock syndrome, mainly in women in which a tampon-associated infection with staphylococci or streptococci results in vasodilation, high fever and rash) ⁷
- Anaphylactic shock ⁷
- Neurogenic shock due to spinal cord injury above Th4 or Th6 ⁵ (low blood pressure, no tachycardia, warm skin, paraplegia or tetraplegia, numbness ²
- Toxic shock (poisoning with nitroprusside, bretylium)
Cardiogenic shock due to heart failure (myocardial infarction, arrhythmia, cardiomyopathy, heart valve disease) ^7,27
Obstructive shock:
- Cardiac tamponade (muffled heart tones, distended neck veins) ^2,7
- Tension pneumothorax (displaced trachea, decreased breathing sounds on one side) ^2,7
- Hemorrhagic pneumothorax
- Pulmonary embolism ²⁷
Arteriovenous malformations ²
Vasodilation as a side effect of drugs, such as barbiturates, nitrates, opiates, antihypertensives (beta blockers, vasodilators) ^7,25,26
Temporary autonomic dysfunction:
- Orthostatic hypotension ⁹
- Vasovagal syncope ¹⁰

The term “relative hypovolemic shock” can be used when the volume of the circulatory system increases due to vasodilation, for example in neurogenic shock, and the volume of the blood remains the same but insufficient to perfuse peripheral organs.

Pathophysiology

Compensated Shock

Shock is compensated until the cardiac output (CO) and systolic blood pressure (BP) remain normal and thus manage to maintain proper perfusion of peripheral tissues.

Baroreceptor reflex. Bleeding or other cause of fluid loss results in a drop of blood volume and hence blood pressure, which is detected by baroreceptors in the aortic and carotid arch. Baroreceptors activate the sympathetic system–sympathetic nerves, which release norepinephrine (noradrenaline) and adrenal medulla, which releases epinephrine (adrenaline)–, which results in the constriction of the peripheral blood vessels in the skin and increased heart contractility and heart rate. The brain, heart and kidney arteries have an ability of autoregulation, which means they can maintain adequate blood perfusion despite a gross reduction of the blood pressure (systolic BP 60-100 mm Hg). All these changes result in the redirection of the blood flow from the skin, muscles and gastrointestinal tract toward the heart, brain and kidneys.
Fluid retention
- Atrial volume receptors sense the drop of the blood volume and stimulate the release of the antidiuretic hormone (ADH) from the pituitary gland, which reduces water excretion through the kidneys.
- Osmoreceptors in the hypothalamus detect the increase of blood osmolality and trigger the release of the ADH ⁸.
- Decreased perfusion of the juxtaglomerular apparatus in the kidneys stimulates renin >> angiotensin I >> angiotensin II and finally aldosterone release from the adrenal cortex, which causes the retention of sodium and hence water in the kidneys, which helps to maintain blood volume.
Movement of fluid from intracellular and interstitial space into the blood.
Bronchodilation and hyperventilation triggered by increased sympathetic activity results in increased oxygen delivery to the tissues.

References ^1,13,23,38

Progressive or Decompensated Shock

Shock is decompensated when cardiac output and blood pressure drop to the point where they can not maintain proper perfusion of the tissues any more. This results in decreased oxygen delivery to the tissues and switch from aerobic to anaerobic metabolism, which results in lactate production and lactic acidosis.

Irreversible Shock

Shock is irreversible when the damage of the vital organs is so extensive that death cannot be prevented despite treatment. The patient can still survive up to three weeks after the onset of irreversible shock ³².

Table 2. Stages (Classes, Grades) of Hypovolemic Shock; Vital Signs
	Compensated		Decompensated
	Stage 1	Stage 2	Stage 3	Stage 4
Blood volume loss	<15% (< 750 mL)	15-30% (750-1,500 mL)	30-40% (1,500-2,000 mL)	>40% (>2,000 mL) (immediately life threatening) 2
Cardiac output	Compensated by constriction of vascular bed	Lower	Lower	Lower
Systolic blood pressure	Normal	Normal	<100 mm Hg	<70 mm Hg
Diastolic blood pressure	Normal	Increased		Often not detectable due to narrow gap between syst and diast BP
Respiratory rate	Normal	Increased (tachypnea)	>30/min	Pronounced tachypnea
Heart rate	Slightly increased but <100/min	>100/min	>120/min	>140/min
Pulse	Normal	Weak	Weak	Weak or absent
Capillary refill	Normal (<2 sec)	Delayed (>2 sec)	Delayed (>2 sec)	Absent
Urine output	Normal (>30 mL/hour)	20-30 mL/hour	<20 mL/hour	Negligible
Skin	Pale	Pale, sweaty	Cool, pale, sweaty	Cool, extremely pale, sweaty
Mental status	Slight anxiety	Slight anxiety, restlessness	Confusion, agitation	Lethargy, coma

Table 2 references: ^2,38

Therapeutical/Physiological Classification of Hemorrhagic Shock

MILD: Normal blood pressure
MODERATE: Low blood pressure that responds to fluid replacement
SEVERE: Low blood pressure that does not respond to fluid replacement test
CRITICAL: >40% blood loss or brain or heart involvement (coma, bradycardia)
Reference: ¹⁶

Early/First Symptoms

Clinical symptoms and signs may not be present until 10-20% of the total blood volume in adults or up to 30% in infants is lost.

Thirst due to hypovolemia (hypovolemic thirst) can appear after 15% blood loss
Nausea
Anxiety, irritability, agitation, sleepiness, confusion
Pale, clammy skin (in dehydration, especially in heat stroke, skin is initially dry and warm)
Symptoms of bleeding: vomiting blood (hematemesis), blood in the stool (melena), blood in the urine, bruising, chest or back pain (rupture of the thoracic aorta), abdominal or flank pain (rupture of the abdominal aortic aneurysm, stabbing), vaginal bleeding outside of menstruation.

Early Signs

Paleness, excessive sweating (diaphoresis)
- NOTE: in heat stroke, the skin would be dry and warm
Dilated pupils
Increased heart rate (tachycardia; may not occur early in patients who take beta-blockers)
Weak, wide pulse, initially due to increased adrenaline release and subsequent peripheral vasoconstriction and increased diastolic blood pressure
Blood pressure may not fall until about 20% blood (in infants 30%) is lost. Older people with high blood pressure or atherosclerosis may be in the stage of decompensated shock even if their blood pressure is at 120 mm Hg or above ¹⁶.
Increased breathing frequency (tachypnea)
Capillary refill time (CRT)
- >2 seconds in infants, children and adults (CRT in healthy, especially in old people can be prolonged in cold ambient)
- >3 sec corresponds to ~10% drop of blood volume
Body weight is decreased in external bleeding and dehydration, but not changed in internal bleeding, septic, anaphylactic or toxic shock.
Early signs of dehydration: poor skin turgor, sunken fontanelle in infants, decrease in body weight
Signs of internal bleeding: abdominal tenderness, swelling, discoloration, guarding, bruising pattern of Grey, Turner sign and Cullen’s sign
Signs of gastrointestinal bleeding: blood in the nose, mouth, throat or rectum (rectal examination).

NOTE: In infants, early symptoms and signs of hypovolemic shock are less obvious than in adults ²³.

Late Symptoms

Early symptoms plus the following:
Dizziness
Fainting
Weakness
Confusion
Lethargy

Late Signs

Early signs plus the following:
Mottled, cyanotic skin
Increase of tachycardia, bradycardia or arrhythmia
Increased breathing rate (tachypnea: >30/min) or decreased breathing rate (bradypnea: <12/min) ²
Capillary refill time (CRT) >5 seconds or absent
Decreased body temperature (hypothermia)
Low, “narrow” blood pressure (systolic pressure falls earlier than diastolic, because it is more dependent on blood volume; systolic blood pressure may not fall until 30% blood is lost).
Decreased or absent urination (<20 mL/hour)
Coma

References: ^{1,2,7,23,29,35}

First Aid (ABC)

Check for airway, breathing, circulation and, if necessary, start with resuscitation (artificial breathing, heart massage).

Do not move a conscious person or his/her head with a suspected spinal cord injury (most possible in head injury, direct blow to the spine, fall from the height, traffic accident).
Move an unconscious person, including the one with a suspected spinal cord injury, into a recovery position. At least two other people should assist you, if possible, to provide minimal twisting of the neck and back.
Call for an ambulance (USA, Canada: 911, UK: 999, Australia: 000, India: 102).

Stopping External Bleeding

Wear gloves, if possible.
If the person does not seem to have an injured spinal cord (intact sensation in the arms and legs), move him/her in a lying position with the bleeding part about 12 inches or 30 cm above the heart, if possible.
Check the wound and remove free foreign objects (sand, cloth, etc.). DO NOT remove or move objects that are stuck in the wound, such as a knife or a sharp piece of wood).
If possible, pull the edges of the wound together and fix them with a bandage
Cover the wound with a gauze and apply pressure with the hands for 20 minutes to stop bleeding (if possible the injured person can do it) ; during this time do not check if the bleeding has stopped. If no gauze is available, use a part of the clothing or a clean plastic bag or bare hands (clean, if possible). If a gauze becomes saturated with the blood do not remove it but add another gauze over it. If the bleeding does not stop apply pressure with your fingers to one of the pressure points (behind the knee or in the groin, on the inner side of the elbow or below the armpit). There are different opinions about using a tourniquet on a bleeding limb: some doctors say not to use a tourniquet or use it as a last resort, others say use at least 2 inches (5 cm) wide tourniquet between the wound and the body until bleeding stops ¹⁴.
If the person feels cold, cover him/her with a blanket.
DO NOT give a person anything to drink or eat, even if he/she is severely thirsty.
Reference: ³³

First Aid in Suspected Internal Bleeding

Internal bleeding may not be visible; it can be suspected in high speed injuries, traffic accidents, falls from the height, after stabbing, etc.

A person with a suspected internal bleeding who does not likely has a spinal injury should lie flat with the feet raised about 12 inches (30 cm) above the level of the heart.
DO NOT give a person anything to drink or eat, even if he/she is severely thirsty ⁵⁰.

Laboratory Tests in Hypovolemia

Initial Tests and Procedures

When internal bleeding is suspected:

Auscultation:
- No lung sounds on one side in pneumothorax/hemothorax
Diagnostic peritoneal lavage
Ultrasonography or CT of the thorax or abdomen
Nasogastric tube and gastric lavage and upper endoscopy
Chest X-ray if perforated ulcer or hemothorax is suspected
Colonoscopy
Angiography
X-ray of limbs, when fractures are suspected
Pregnancy test, when ectopic pregnancy is suspected
Central vein catheter
Thoracic tube to drain hemothorax
ECG can be done to exclude heart attack or other causes of cardiogenic shock.
References: ^4,31,40

Monitoring of Hemodynamic Changes

ECG to exclude cardiogenic shock.
Central Venous Pressure (CVP) <4 mm Hg (<5 mm water) indicates hypovolemia ³⁵
Pulmonary Artery Occlusion Pressure (PAOP) also called Pulmonary Wedge Pressure (PWP) or Pulmonary Capillary Wedge Pressure (PCWP) is usually decreased ³⁸
Cardiac Output (CO) is reduced ²³.
References: ^23,35,38

Blood Tests:

CBC in bleeding is initially normal.
Hemoglobin (Hb) can be low in chronic bleeding, but not in the first hours of acute bleeding.
Hematocrit (HCT):
- Normal up to eight hours after onset of bleeding. After 8-12 hours, the redistribution of the interstitial fluid into the blood occurs, so HCT and Hb fall.
- Increased in fluid loss without red cell loss:
  - Dehydration (diarrhea, vomiting, polyuria, excessive sweating)
  - Plasma loss (burns)
Sodium (Na):
- Normal in bleeding (initially)
- Decreased in hypovolemic hyponatremia
Potassium (K)
Chloride (Cl)
Blood Urea Nitrogen (BUN) can be increased in dehydration, gastrointestinal bleeding, rhabdomyolysis, urinary outlet obstruction or sepsis ¹⁷
Creatinine: normal, except in renal failure ^23,31
Urea: normal, except in renal failure ³¹
Glucose levels: initially hyperglycemia (gluconeogenesis, glycogenolysis due to increased epinephrine), later hypoglycemia (due to glycogen exhaustion) ³⁸
Bleeding time: prolonged in late shock
Activated partial thromboplastin time (aPPT): prolonged in coagulation disorders ³¹
Prothrombin time (PT): prolonged in coagulation disorders ³¹
Arterial blood gases (ABGs):
- pH<7.3 = acidosis ³¹
- Respiratory alkalosis progressing to metabolic acidosis (due to lactic acidosis) ¹³
- Metabolic acidosis can also occur in severe diarrhea ²³
- HCO3^–(bicarbonate) is decreased in metabolic acidosis
- Base deficit increases (become more negative) with acidosis which increases with the extent of hypovolemia (mild base deficit: 2 to -5; moderate: -6 to -14; over -15) ³⁰. Base deficit is usually expressed as a negative base excess (BE). So, base deficit can be used as a guide for fluid resuscitation.

Urine Tests

Urine specific gravity is usually increased ²³
hCG (pregnancy test) to test for ectopic pregnancy ²³

Treatment

The following is an overview of the usual procedures and it is not meant as treatment instructions.

1. Ventilation

In a decompensated shock, 100% oxygen should be given by a non-rebreathable facial mask ²⁵.

2. Immobilization

Immobilization of the neck spine and limbs in a patient with trauma should be done before transport.

3. Transport

The patient should be transported to the hospital as soon as possible.

The first goal in treatment of hypovolemic shock is to correct hypotension ³⁸.

4. Fluid Deficit Replacement

Fluid deficit replacement can start during transport ^35,38,40. Fluids, which should be warmed, should be given via 2 large bore i.v. lines. The following fluids can be used ⁴¹:

Crystalloids (3 liters are needed to restore 1 liter of lost blood).
- Isotonic saline (0.9% NaCl)
- Ringer lactate
Colloids (1 liter is needed to restore 1 liter of lost blood):
- Hetastarch
- Pentastarch
- Albumin
- Dextran
Blood products (when 2,000 mL crystalloids does not help):
- Fresh frozen plasma (FFP)
- Packed red blood cells (PRBCs)
- Whole blood transfusion
Products to assist normal blood function:
- Tranexamic acid (decreases mortality)
- Recombinant human factor VIIa
- Prothrombin complex

NOTE: Using large amounts of fluid before surgery has been questioned lately ¹⁶.

5. Stopping Internal Bleeding

Internal bleeding can be reduced by certain drugs or stopped by an immediate surgery.

Gastrointestinal bleeding ⁴⁰:
- Intravenous H2 blockers
- Vasopressin (can have severe side effects)
- Somatostatin, octreotide
- Surgery

6. Medications

Vasoconstrictors–medications that increase blood pressure should not be given before hypovolemia has been corrected by fluids. There is insufficient evidence in using vasoconstrictors in improving survival in the acute phase of trauma ⁸.

Norepinephrine (Noradrenaline)

Norepinephrine is released from the nerve endings of sympathetic nerves. It stimulates alpha 1 and beta 1 receptors and causes peripheral vasoconstriction, increases heart rate and contractility and rises both systolic and diastolic blood pressure ³². Norepinephrine as a drug can be used in acute fall of the blood pressure.

Epinephrine (Adrenaline)

Adrenaline stimulates alpha 1 and beta 1 receptors. It causes peripheral vasoconstriction, increases heart rate and contractility and systolic blood pressure ³².

Other Possible Medications:

Dopamine in high doses, which increases vasoconstriction (dopamine in low doses causes vasodilation) ¹⁶
Phenylephrine
Dobutamine
Isoproterenol
Milrinone

Complications

Multiple Organ Dysfunction Syndrome (MODS)
Lungs: Acute Respiratory Distress Syndrome (ARDS)
Kidneys: Acute tubular necrosis resulting in acute renal failure
Heart: heart attack (myocardial infarct)
Brain: seizures (in hypovolemic hyponatremia and heat stroke)
Blood: disseminated intravascular coagulation (DIC) due to hypothermia and acidosis
Gastrointestinal tract: stress ulcers, ileus, ischemic bowel (“dead gut”), leaky gut syndrome, abdominal compartment syndrome
Liver necrosis
Limbs: gangrene
Hypothermia (due to low tissue perfusion, cold intravenous fluids, cold environment)
Hyperthermia (in heat stroke or sepsis)
Hemorrhagic shock and encephalopathy syndrome in infants and children (rare) (high fever, seizures)
References: ^7,13,23,39

Prognosis

Prognosis of hypovolemic shock mainly depends on the volume of blood lost, the speed of fluid replacement and underlying health conditions.

References

Hypovolemic Shock

What Is Hypovolemic Shock: Definition

Causes and Risk Factors

Differential Diagnosis

Pathophysiology

Compensated Shock

Progressive or Decompensated Shock

Irreversible Shock

Table 2. Stages (Classes, Grades) of Hypovolemic Shock; Vital Signs

Compensated

Decompensated

Stage 1

Stage 2

Stage 3

Stage 4

Blood volume loss

Cardiac output

Systolic blood pressure

Diastolic blood pressure

Respiratory rate

Heart rate

Pulse

Capillary refill

Urine output

Skin

Mental status