Interdisciplinary Medicine

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Trauma (e.g., crush syndrome, burns, electrical shock)

Muscle ischemia (e.g., thrombosis, embolism, vasculitis, sickle cell disease, pressure necrosis, tourniquet shock)

Drugs: Drug-induced rhabdo can occur through several mechanisms.

• Primary, toxin induced (e.g., ethanol, methadone, ethylene glycol, isopropyl alcohol, CO poisoning)

• Long-term intake of drugs associated w/hypokalemia (e.g., thiazides)

• OD of certain drugs (e.g., barbiturates, heroin, cocaine)

• Malignant hyperthermia (usually seen in genetically predisposed individuals, after exposure to halothane, succinylcholine, or pancuronium)

• NMS (associated w/use of phenothiazines, butyrophenones, antipsychotics, cocaine, or diphenhydramine, usually in pts w/dehydration and electrolyte imbalance)

• Use of certain lipid-lowering agents (e.g., combination of statins and gemfibrozil, or erythromycin and simvastatin; and amiodarone; amphetamines, haloperidol)

• Direct myotoxicity (e.g., colchicine, zidovudine, cyclosporine, itraconazole)

Infections

• Bacterial (e.g., Streptococcus, Salmonella, Clostridium, Legionella, Leptospira, Shigella)

• Viral (e.g., echo, coxsackie, influenza, CMV, herpes, EBV, hepatitis)

• Parasites (trichinosis)

Excessive muscle stress (e.g., marathon runners, status epilepticus, delirium tremens)

Genetic defects (carnitine deficiency, phosphorylase deficiency, glucosidase deficiency, cytochrome disturbances)

Miscellaneous: brown recluse spider bite, snake bite, hornet sting, polymyositis, dermatomyositis, heat stroke, DKA, hyponatremia, hypophosphatemia, myxedema, thyroid storm, RMSF, hypothermia, CO, cyclic antidepressants, phenylpropanolamine, codeine, phencyclidine (PCP), amphetamines, LSD, Reye’s syndrome

Diagnosis

H&P

Variable muscle tenderness. Rhabdo apart from statin use is manifested w/muscle sx only 50% of the time.

Weakness

Muscle rigidity

Fever

Altered consciousness

Muscle swelling

Malaise, fatigue. In statin-induced rhabdo, fatigue (74%) is nearly as common as muscle pain (88%).

Dark urine (secondary to myoglobin in urine, will make dipstick false (+) for RBC’s)

Labs

↑↑ CK: Elevations may exceed 100,000 U/L in fulminant rhabdo; the development of renal failure is not directly related to the threshold level of CK; isoenzyme fractionation is useful: if CK-MB >5% of the total CK, involvement of the myocardium is likely.

↑Serum Cr: The etiology of the renal failure is uncertain and probably multifactorial (renal tubular obstruction by precipitated myoglobin, direct myoglobin toxicity, hypotension, dehydration, ↓ GFR, intravascular coagulation).

Serum K⁺: Preexisting hypokalemia is a contributing factor to rhabdo; fulminant rhabdo can result in life-threatening hyperkalemia secondary to ↑ K⁺ release from damaged muscle and impaired renal excretion.

Ca²⁺ and PO₄^-3: Initially, pts have hyperphosphatemia from muscle necrosis, secondary hypocalcemia from Ca²⁺ deposition in the injured muscle, and ↓ 1,25-dihydroxycholecalciferol; later (in the diuretic phase of renal failure), hypercalcemia is present as a result of remobilization of the deposited Ca²⁺ and secondary hyperparathyroidism.

Myoglobin: This is present in the serum and urine; the urine is brownish, has granular casts, and is O-toluidine(+); a quick visual method to separate myoglobinuria from hemoglobinuria is to examine the urine and serum simultaneously: reddish brown urine and pink serum indicate hemoglobinuria, whereas brown urine and clear serum suggest myoglobinuria; ↑ in serum myoglobin precedes the ↑ in CK level and is useful to estimate the risk of renal failure (serum myoglobin levels >2000 μg/L may be associated w/renal insufficiency).

Treatment

Vigorous fluid replacement is given to maintain a good urinary output, at least until myoglobin disappears from the urine. Initially NS should be given at a rate of 1.5 L/hr w/close monitoring of cardiac, pulmonary, and electrolyte status. Maintain ↑ rate of IV fluids at least until CPK <1000 U/L. Pts may require >15 L of fluid in the initial 24 hr to achieve urine flow rates of 200 to 300 mL/hr.

Administration of a single dose of mannitol (100 mL of a 25% solution IV during 15 min) remains controversial. Mannitol acts as an osmotic diuretic, renal vasodilator, and intravascular volume expander and may convert oliguric renal failure to nonoliguric.

Alkalinization of the urine w/addition of 44 mEq/L of NaHCO₃ is advocated by some experts. The goal is to maintain urine pH >6.5. NaHCO₃ may ↑ solubility of uric acid and myoglobulin; however, it may promote Ca deposition.

Hyperkalemia caused by rhabdo is most severe 10 to 40 hr after injury; initial treatment w/sodium polystyrene sulfonate may be indicated; hyperkalemia caused by rhabdo responds poorly to treatment w/glucose and insulin; attempts to correct hyperkalemia and initial hypocalcemia w/Ca infusion may result in metastatic calcifications and severe hypercalcemia in the recovery period; hemodialysis may be necessary in pts w/severe hyperkalemia, volume overload, uremic pericarditis, or uremic encephalopathy.

Clinical Pearls

The average length of time on statin Rx before rhabdo is 1 yr. The average time to onset of rhabdo after addition of fibrate to statin Rx is 32 days.

Statin-induced rhabdo is 12× more frequent when statins are combined w/fibrates compared w/statin monoRx.

B. Shock

Figure 13-1 defines shock and its various causes.

Box 13-1 describes the physical exam and selected lab signs in shock.

Table 13-1 illustrates the physiologic response and basic Rx of shock.

Figure 13-2 is an algorithmic approach to the general hemodynamic management of shock.

Table 13-2 describes the action of various vasopressor agents used in shock.

C. Hypothermia

Definition

Rectal temperature <35° C (95.8° F). Accidental hypothermia is unintentionally induced in ↓ core temperature in absence of preoptic anterior hypothalamic conditions.

Diagnosis

H&P

The clinical presentation varies w/the severity of hypothermia; shivering may be absent if body temperature is <33.3° C (92° F) or in pts taking phenothiazines.

Hypothermia may masquerade as CVA, ataxia, or slurred speech, or the pt may appear comatose or clinically dead.

Physiologic stages of hypothermia:

• Mild hypothermia (32.2° C-35° C [90° F-95° F]): arrhythmias, ataxia

• Moderate hypothermia (28° C-32.2° C [82.4° F-90° F]): progressive ↓ of level of consciousness, pulse, CO, and respiration; fibrillation, dysrhythmias (susceptibility to VT); elimination of shivering mechanism for thermogenesis

FIGURE 13-1 Shock. (From Goldman L, Schafer AI [eds]: Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)

TABLE 13-1

Types of Shock, Physiologic Response, and Basic Treatment

Type of Shock	HR	Preload	Contractility	SVR	Treatment
Hypovolemic	↑	↓↓	±	↑	High-flow oxygen Fluid resuscitation: evaluate perfusion after 60 mL/kg total volume bolused, then consider pressors
Septic (early, warm)	↑	↓↓	±	↓	High-flow oxygen Fluid resuscitation Antibiotics Pressors (dopamine, norepinephrine, phenylephrine)
Septic (late, cold)	↑	↓↓	↓	↑	High-flow oxygen Fluid resuscitation Antibiotics Pressors (dopamine, norepinephrine, phenylephrine)
Anaphylactic	↑	↓↓	↓	↓	High-flow oxygen Epinephrine (IM) Fluid resuscitation
Neurogenic	↑	↓↓	±	↓↓	Fluid resuscitation Pressors (norepinephrine)
Cardiogenic	↑	↑	↓↓	↑	High-flow oxygen Fluid resuscitation (5-10 mL/kg) CHF management (CPAP/BiPAP, diuretics, ACE inhibitors) Inotropes (milrinone, dobutamine)
Obstructive	Cause dependent	Cause dependent	Cause dependent	Cause dependent	Therapy directed at primary etiology of shock

From Tschudy MM, Arcara KM: The Harriet Lane Handbook, 19th ed. Philadelphia, Mosby, 2012.

Box 13-1 Physical Examination and Selected Laboratory Signs in Shock

Central nervous system	Acute delirium, restlessness, disorientation, confusion, and coma, which may be secondary to decreased cerebral perfusion pressure (mean arterial pressure minus intracranial pressure). Pts with chronic hypertension or increased intracranial pressure may be symptomatic at normal blood pressures. Cheyne-Stokes respirations may be seen with severe decompensated heart failure. Blindness can be a presenting complaint or complication.
Temperature	Hyperthermia results in excess tissue respiration and greater systemic oxygen delivery requirements. Hypothermia can occur when decreased systemic oxygen delivery or impaired cellular respiration decreases heat generation.
Skin	Cool distal extremities (combined low serum bicarbonate and high arterial lactate levels) aid in identifying pts with hypoperfusion. Pallor, cyanosis, sweating, and decreased capillary refill and pale, dusky, or clammy extremities indicate systemic hypoperfusion. Dry mucous membranes and decreased skin turgor indicate low vascular volume. Low toe temperature correlates with the severity of shock.
General cardiovascular	Neck vein distention (e.g., heart failure, pulmonary embolus, pericardial tamponade) or flattening (e.g., hypovolemia), tachycardia, and arrhythmias. Decreased coronary perfusion pressures can lead to ischemia, decreased ventricular compliance, and increased left ventricular diastolic pressure. A “mill wheel” heart murmur may be heard with an air embolus.
Heart rate	Usually elevated. However, paradoxical bradycardia can be seen in pts with preexisting cardiac disease and severe hemorrhage. Heart rate variability is associated with poor outcomes.
Systolic blood pressure	May actually increase slightly when cardiac contractility increases in early shock and then fall as shock advances. A single episode of undifferentiated hypotension with a systolic blood pressure <80 mm Hg carries an in-hospital mortality of 18%.
Diastolic blood pressure	Correlates with arteriolar vasoconstriction and may rise early in shock and then fall when cardiovascular compensation fails
Pulse pressure	Defined as systolic minus diastolic pressure and related to stroke volume and the rigidity of the aorta. It increases early in shock and decreases before systolic pressure decreases.
Pulsus paradoxus	An exaggerated change in systolic blood pressure with respiration (systolic blood pressure declines >10 mm Hg with inspiration) seen in asthma, cardiac tamponade, and air embolus
Mean arterial blood pressure	Diastolic blood pressure + [pulse pressure/3]
Shock index	Heart rate/systolic blood pressure. Normal = 0.5 to 0.7. A persistent elevation of the shock index (>1.0) indicates impaired left ventricular function (as a result of blood loss and/or cardiac depression) and is associated with increased mortality.
Respiratory	Tachypnea, increased minute ventilation, increased dead space, bronchospasm, hypocapnia with progression to respiratory failure, acute lung injury, and adult respiratory distress syndrome
Abdomen	Low-flow states may result in abdominal pain, ileus, gastrointestinal bleeding, pancreatitis, acalculous cholecystitis, mesenteric ischemia, and shock liver
Renal	Because the kidney receives 20% of cardiac output, low cardiac output reduces the glomerular filtration rate and redistributes renal blood flow from the renal cortex toward the renal medulla, leading to oliguria. Paradoxical polyuria in sepsis may be confused with adequate hydration.
Metabolic	Respiratory alkalosis is the first acid-base abnormality, but metabolic acidosis occurs as shock progresses. Hyperglycemia, hypoglycemia, and hyperkalemia may develop.

From Goldman L, Schafer AI (eds): Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.

• Severe hypothermia (<28° C [82.4° F]): absence of reflexes or response to pain, ↓ cerebral blood flow, ↓ CO₂, risk of VF or asystole

Labs

Metabolic acidosis and respiratory acidosis are usually present. ↓ K+ initially, then ↑ K+ w/↓ temp; extreme hyperkalemia indicates a poor prognosis; ↓ Hct (caused by hemoconcentration), ↓ leukocytes, ↓ Plt (caused by splenic sequestration), ↑ clotting time

Imaging

CXR: generally not helpful; may reveal evidence of aspiration (e.g., intoxicated pt w/aspiration pneumonia)

ECG (Fig. 13-3): ↑ PR, QT, and QRS segments; ↑ ST segments, inverted T waves, AV block; hypothermic J waves (Osborn waves), characterized by notching of the junction of the QRS complex and ST segments, may appear at 25° C to 30° C.

Treatment

Secure an airway before warming all unconscious pts; precede ETT w/oxygenation (if possible) to ↓ the risk of arrhythmias during the procedure.

Peripheral vasoconstriction may impede placement of a peripheral IV catheter; consider femoral venous access as an alternative to the jugular or subclavian sites to avoid ventricular stimulation.

A Foley catheter should be inserted, and urinary output should be monitored and maintained >0.5 to 1 mL/kg/hr w/intravascular volume replacement.

Continuous ECG monitoring of pts is recommended; consider ventricular arrhythmia Rx w/bretylium; lidocaine is generally ineffective, and procainamide is associated w/incidence of VF in hypothermic pts.

FIGURE 13-2 General hemodynamic management. DO₂, (system) oxygen delivery; PAOP, pulmonary artery occlusion pressure; pHi, intestinal mucosal pH; PPV, pulse pressure variation; SVV, stroke volume variation; VO₂, (systemic) oxygen consumption. (From Goldman L, Schafer AI [eds]: Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)

FIGURE 13-3 Hypothermic J waves. (From Ferri F, Practical Guide to the Care of the Medical Patient, 8th ed, St. Louis, Mosby 2011)

TABLE 13-2

Vasopressor Agents

Agent	Dose Range	Peripheral Vasculature		Cardiac Effects			Typical Use
Agent	Dose Range	Vasoconstriction	Vasodilation	HR	Contractility	Dysrhythmias	Typical Use
Dopamine	1-4 μg/kg/min	0	1+	1+	1+	1+	“Renal dose” does not improve renal function; may be used with bradycardia and hypotension
	5-10 μg/kg/min	1-2+	1+	2+	2+	2+
	11-20 μg/kg/min	2-3+	1+	2+	2+	3+	Vasopressor range
Vasopressin	0.04-0.1 U/min	3-4+	0	0	0	1+	Septic shock, post–cardiopulmonary bypass shock state; no outcome benefit in sepsis
Phenylephrine	20-200 μg/min	4+	0	0	0	1+	Vasodilatory shock; best for supraventricular tachycardia
Norepinephrine	1-20 μg/min	4+	0	2+	2+	2+	First-line vasopressor for septic shock, vasodilatory shock
Epinephrine	1-20 μg/min	4+	0	4+	4+	4+	Refractory shock, shock with bradycardia, anaphylactic shock
Dobutamine	1-20 μg/kg/min	1+	2+	1-2+	3+	3+	Cardiogenic shock, septic shock
Milrinone	37.5-75 μg/kg bolus followed by 0.375-0.75 μg/min	0	2+	1+	3+	2+	Cardiogenic shock, right heart failure; dilates pulmonary artery; caution in renal failure