domingo, 9 de septiembre de 2012

Radiographic Challenge

A 66-year-old woman is admitted with vague abdominal pain and vomiting. ¿What is your diagnose?

jueves, 5 de julio de 2012

Clinical Challenge

A 29-year-old man presented to a local hospital with a 1-week history of intermittent fever, drenching night sweats, reduced appetite, and left upper abdominal pain exacerbated by inspiration. He reported no weight loss, cough, dyspnea, nausea, diarrhea, rash, mouth ulcers, arthralgias, or ocular or urinary symptoms.
Eight years previously, the patient had an episode of fever, with raised inflammatory markers that persisted for 12 weeks. He underwent evaluation for cancer and infection, including tuberculosis, but no cause was identified. Joint pains subsequently developed, and he had a positive antinuclear antibody test, at a low titer; he was treated with oral glucocorticoids over a period of 2 months, with resolution of his symptoms. He no longer took any medications. He was born in the United Kingdom to Indian parents, lived with his wife in London, and worked as a management consultant. He traveled to India occasionally; the last trip was 4 years earlier. He had never smoked, had minimal alcohol intake, and noted no risk factors for human immunodeficiency virus (HIV) infection. His father had died of an aggressive natural killer cell leukemia. There was no family history of autoimmune or clotting disorders.

Clinical examination confirmed a temperature of 38.2°C, but the patient appeared well. The blood pressure was 125/64 mm Hg, and the pulse was 92 beats per minute and regular. Heart sounds were normal, and chest sounds were clear. There was no hepatosplenomegaly, lymphadenopathy, abdominal tenderness, or mass. He was alert and oriented, with no weakness or sensory deficits. There was no rash and no joint erythema or swelling.

The white-cell count was 2500 per cubic millimeter, with 62% (1540) neutrophils, 22% (560) lymphocytes, 15% (380) monocytes, <1% basophils, and <1% eosinophils. The hemoglobin level was 11.5 g per deciliter, and the platelet count 107,000 per cubic millimeter. The reticulocyte count was 0.3% (normal range, 0.5 to 1.5). The prothrombin time was 14.2 seconds (normal range, 9.6 to 11.6), and the activated partial-thromboplastin time was 75.4 seconds (normal range, 24 to 32), with a corrected value of 61.3 seconds on mixing with normal plasma. The serum sodium level was 127 mmol per liter, potassium 3.9 mmol per liter, blood urea nitrogen 8.1 mg per deciliter (2.9 mmol per liter), and creatinine 1.2 mg per deciliter (106 μmol per liter). Liver-function tests and the serum amylase level were normal. The erythrocyte sedimentation rate was 88 mm in the first hour, and the C-reactive protein was 0.8 mg per deciliter (normal value, <0.5). Blood cultures were obtained.
Tests for antinuclear antibodies and anti-dsDNA antibodies were positive, both at a titer of 1:320. Tests for anti-Sm, anti-Ro, and anti-La antibodies were negative. The C3 level was 0.54 g per liter (normal value, >0.7), and the C4 level was 0.07 g per liter (normal value, >0.16). Testing for the lupus anticoagulant was positive. A test for anticardiolipin IgG antibodies was reported to be moderately positive, and a test for IgM antibodies was negative. Urine sediment and serum creatinine levels remained normal.
It was performed another diagnostic tests. What would be your diagnose and your management?

You came the next day to watch your patient results and find these information (the lab results that you ordered are underligned) :

The patient was treated with intravenous amoxicillin and clavulanate but continued to have spiking fevers daily, with peak temperatures of more than 38.5°C. Over the next 2 days, headaches, confusion, and muscle cramps developed, as well as proteinuria (1.78 g of protein per liter), and he was transferred to a tertiary care hospital. Chest radiography and magnetic resonance imaging of the brain showed no abnormalities. A lumbar puncture revealed normal opening pressure. Cerebrospinal fluid protein and glucose levels were normal, and no cells were seen on microscopy. CT imaging of the chest, abdomen, and pelvis showed no abnormalities. The platelet count fell to 12,000 per cubic millimeter, and the neutrophil count to 290 per cubic millimeter.

Blood and urine cultures were negative, as were serologic tests for HIV types 1 and 2, human T-cell lymphotrophic virus, hepatitis B virus, hepatitis C virus, varicella–zoster virus, herpes simplex virus, Coxiella burnetii, brucella, mycoplasma, Chlamydophila psittaci, legionella, and toxoplasma. Polymerase-chain-reaction assays for respiratory syncytial virus, influenza virus, parvovirus B19, CMV, EBV, human herpesvirus 6, and human herpesvirus 8 were negative, as was an enzyme-linked immunosorbent spot assay for tuberculosis.

The serum ferritin level was 105,506 μg per liter (normal range in men, 30 to 400), fasting triglycerides 494 mg per deciliter (5.58 mmol per liter; normal value, <177 [<2]), and fibrinogen 0.98 g per liter (normal range, 1.8 to 3.6). Repeated blood and urine cultures were sterile. Bone marrow aspiration and trephine biopsy revealed macrophage proliferation and phagocytosis of hematopoietic cells of erythroid, myeloid, and megakaryocytic lineages.

With all these information what would be your diagnose?

The serum ferritin level was 105,506 μg per liter (normal range in men, 30 to 400), fasting triglycerides 494 mg per deciliter (5.58 mmol per liter; normal value, <177 [<2]), and fibrinogen 0.98 g per liter (normal range, 1.8 to 3.6). Repeated blood and urine cultures were sterile. Bone marrow aspiration and trephine biopsy revealed macrophage proliferation and phagocytosis of hematopoietic cells of erythroid, myeloid, and megakaryocytic lineages.

Treatment with intravenous methylprednisolone (1 g daily for 3 days) and intravenous immune globulin (2 g per kilogram of body weight over a period of 2 days) was initiated, and the antimicrobial regimen was broadened to include intravenous meropenem and acyclovir, with oral fluconazole as antifungal prophylaxis. The patient was given red-cell and platelet transfusions. The fever subsided, but the pancytopenia persisted, and he had ongoing difficulties with attention and short-term memory. Mycophenolate mofetil (1 g twice daily) was added, with subsequent improvement in his cytopenias and cognitive function.

The patient's glucocorticoid treatment was gradually tapered, and he was discharged from the hospital while taking oral prednisolone and mycophenolate mofetil. At the time of discharge, his white-cell count and hematocrit were normal; he had mild thrombocytopenia, which resolved over the next 6 weeks. The patient's condition steadily improved, and all immunosuppressive treatment was progressively withdrawn over the next 2 years. He has resumed full-time work and remained well at a 3-year follow-up visit.


This case highlights two important and related causes of fever and pancytopenia: SLE and the hemophagocytic syndrome. The features that prompted consideration of SLE in this patient were fever, abdominal pain suggestive of serositis, proteinuria, and pancytopenia. The presence of antinuclear antibodies, anti-dsDNA antibodies, and the lupus anticoagulant confirmed the diagnosis.
SLE is frequently associated with fever and with cytopenias. Both findings may reflect underlying disease activity, but additional causes should be considered if these manifestations are severe or prolonged. In this patient, the combination of relentless fever and severe, rapidly progressive pancytopenia suggested overwhelming infection or secondary hemophagocytic syndrome. The poor response to antimicrobial agents and the very high ferritin levels prompted bone marrow examination, which confirmed secondary hemophagocytic syndrome.
Secondary hemophagocytic syndrome, sometimes known as the macrophage activation syndrome, can present at any age and is a rare complication of infection, hematologic cancer, drug exposure (particularly exposure to immunomodulatory drugs), and autoimmune disease. The most common infectious trigger is EBV, but HIV is increasingly implicated, and many other viral, bacterial, and protozoal infections have also been associated with secondary hemophagocytic syndrome.1,2
Of the autoimmune diseases associated with the hemophagocytic syndrome in adults, SLE is by far the most common, accounting for about 60% of cases; the estimated prevalence of the hemophagocytic syndrome among patients with SLE is up to 2.4%.3,4 Adult-onset Still's disease is responsible for 10 to 15% of cases.4,5 There is considerable overlap between the features of adult-onset Still's disease and those of secondary hemophagocytic syndrome, and the possibility of hemophagocytosis should be considered in any patient with adult-onset Still's disease in whom cytopenias develop.6
The mechanisms underlying secondary hemophagocytic syndrome are poorly understood. However, studies indicate that some cases are associated with heterozygous mutations and polymorphisms in the genes responsible for familial hemophagocytic lymphohistiocytosis, a primary disorder that usually presents in infancy.7-9 The identified mutations are associated with defective killing by cytotoxic lymphocytes and natural killer cells, and it is postulated that defective clearance of antigen or antigen-presenting cells leads to persistent stimulation of the immune response and a consequent cytokine storm, resulting in many of the manifestations of this condition.10 High levels of interleukin-1, interleukin-6, TNF, and interferon-γ cause fever, up-regulate ferritin transcription and secretion, and induce cytopenias through myelosuppression rather than through the phagocytosis that is the morphologic hallmark of the disorder.11
There are no validated diagnostic criteria for secondary hemophagocytic syndrome, but suggestive features include high temperatures, organomegaly, cytopenias and coagulopathy, markedly elevated ferritin levels, hypertriglyceridemia, and hypofibrinogenemia. Bone marrow examination usually shows hemophagocytosis, but this finding may initially be absent or confined to other organs, such as the spleen or lymph nodes.12
Data from clinical trials are lacking to guide decisions about specific therapy in adults, and management of secondary hemophagocytic syndrome is based on control of the cytokine storm, treatment of possible triggers, and supportive care. In patients with associated autoimmune diseases, immunosuppression may be indicated. Reports on case series have described good outcomes in patients treated with a variety of immunosuppressive agents, including glucocorticoids (the most commonly used agents for this condition), cyclophosphamide, cyclosporine, and intravenous immune globulin3,13; the use of etoposide, biologic agents, and plasmapheresis has been reported in refractory cases.11 Caution must be exercised in prescribing immunosuppressive therapy, since infectious triggers are identified in more than 50% of these patients,5 and concurrent antimicrobial therapy should be considered.
In three case series of adults with autoimmune diseases and secondary hemophagocytic syndrome, mortality rates ranged from 7 to 38%.3-5 Reported predictors of death included a C-reactive protein level greater than 5 mg per deciliter, a platelet count below 50,000 per cubic millimeter, the presence of infection, and prior use of glucocorticoids. Our patient had severe thrombocytopenia but did not have other features associated with a poor prognosis.
This case highlights the importance of considering additional possibilities when findings are atypical for an established condition. Once a diagnosis of SLE had been made, the crucial next step was to recognize that the ongoing fevers and pancytopenia indicated another diagnosis, secondary hemophagocytic syndrome. Rapid identification of this life-threatening complication of SLE facilitated early aggressive management and resulted in a good clinical outcome.

domingo, 3 de junio de 2012

R.S.I - Rapid Sequence Intubation - Review

rationale behind RSI is to prevent aspiration and its potential problems, including aspiration
pneumonia, and to counteract the increase in systemic arterial blood pressure,
heart rate, plasma catecholamine release, intracranial pressure (ICP), and
intraocular pressure (IOP) that occurs with endotracheal intubation.
RSI generally consists of seven steps: (1) preparation, (2) preoxygenation, (3) pretreatment,
(4) paralysis with induction, (5) protection and positioning, (6) placement of the
tube in the trachea, and (7) postintubation management.
oxygen, suction,
bag-valve mask (BVM), laryngoscope and blades, endotracheal (ET) tubes with a stylet
with one size larger and smaller than the anticipated ET size, resuscitation equipment,
and supplies for rescue maneuvers (eg, laryngeal mask airways [LMA] or cricothyrotomy.
1. Suction, Oxygen, Airway, Pharmacology, Monitoring, Equipment.
2. Preoxygenation should be occurring during the preparation step. The purpose of preoxygenation
is to replace the nitrogen in the patient’s functional residual capacity
(FRC) with oxygen or ‘‘nitrogen wash-out oxygen wash-in.’’ ‘‘Denitrogenation’’ can
be accomplished in 3 to 5 minutes by having the patient breathe 100% oxygen via
a tight-fitting facemask or, if time is an issue, with four vital capacity breaths. positive pressure ventilation should be
avoided during the preoxygenation step because of a risk for gastric insufflation
and possible regurgitation. Because effective ventilation by the patient is not feasible
in many ED patients, BVM ventilation may be necessary in apneic patients or patients
with ineffective spontaneous breathing. In these instances, use of the Sellick procedure
with gentle cricoid pressure should be applied in an attempt to limit gastric distention
and avoid aspiration during BVM ventilation. In the preoxygenation phase, replacing the nitrogen reservoir in the lungs with oxygenallows 3 to 5 minutes of apnea without significant hypoxemia in the normoxic
3. Ancillary medications are administered during the pretreatment step to mitigate the
negative physiologic responses to intubation. For maximal efficacy, the pretreatment
drugs should precede the induction agent by 3 minutes, although this is not always
possible. The pretreatment phase and preoxygenation phase can (and usually) do occur
simultaneously during most instances of RSI in the ED. Medications and their usual
dosages that may be given during the pretreatment phase are lidocaine 1.5 mg/kg,
fentanyl 2–3 mcg/kg, and atropine 0.02 mg/kg (minimum 0.1 mg, maximum 0.5 mg.
The clinical indications for these drugs are (1) for patients with elevated ICP and impaired
autoregulation: administer lidocaine and fentanyl, (2) patients with major vessel
dissection or rupture or those with significant ischemic heart disease give fentanyl, (3)
adults with significant reactive airway disease, premedicate with lidocaine, and (4) atropine
is indicated for pediatric patients %10 years old and in patients with significant
bradycardia if succinylcholine is given. One caveat to remember is to give fentanyl with
caution to any patient in shock (whether compensated or uncompensated) who is dependent
on sympathetic drive because of a potential decrease in blood pressure with
fentanyl administration.
In patients who are receiving succinylcholine as their induction agent and who are at
risk for increased ICP, one tenth of the normal paralyzing dose of a nondepolarizing
(ND) neuromuscular blocking agent (NMB) can be given 3 minutes before receiving
succinylcholine. The purpose of the defasciculating dose of the ND-NMB is to prevent
the fasciculations (and therefore, the increase in ICP) that occurs with succinylcholine.
For example, the dose would be 10% of the paralyzing dose of rocuronium (10% of 0.6
mg/kg 5 0.06 mg/kg). The mnemonic ‘‘LOAD’’ has been used to indicate the pretreatment
drugs for RSI: L 5 lidocaine, O 5 opioid (specifically, fentanyl), A 5 atropine, and
D 5 defasciculation.
Paralysis with induction is achieved by the rapid intravenous administration in quick
succession of the induction agent and the NMB. The selection of a specific sedative
depends on multiple factors: the clinical scenario, which includes patient factors (includes
cardiorespiratory and neurologic status, allergies, comorbidity) and the clinician’s
experience/training and institutional factors, as well as the characteristics of
the sedative.28 Sedatives commonly used for induction during RSI are barbiturates
(pentobarbitol, thiopental, and methohexitol),29 opioids (fentanyl),1 dissociative anesthetics
(ketamine),30 and nonbarbiturate sedatives (etomidate,31 propofol,32 and the
benzodiazepines).21,33 The dosages and characteristics of these agents and are summarized
in Table 1. One caveat to remember is that the induction dosages of these
sedatives may be different (generally, slightly higher) than the dose used for sedation.
For example, for etomidate the usual dose for procedural sedation is 0.2 mg/kg and for
RSI is 0.3 mg/kg.
5.Several caveats regarding the proper technique need to be considered: location,
timing, and amount of pressure. Cricoid pressure should be applied as soon as the patient
starts to lose consciousness and should be maintained until the correct endotracheal
position is verified. Pressure should be gentle but firm enough to compress the
esophagus between the cricoid cartilage and the anterior surface of the vertebral
body. The cricoid cartilage is opposite the C4–C5 vertebrae in an adult, and C3–C4
in an infant.
Step 6—Placement of the Endotracheal Tube in the Trachea
When the jaw becomes flaccid from the paralytics, it is time to begin intubation by
standard methods. ET tube placement should be confirmed by the usual techniques.
Step 7—Postintubation Management
After ET tube placement and confirmation, the ET tube must be secured. A chest radiograph
is done not only to check for proper ET tube placement but also to evaluate
the pulmonary status and to monitor for any complications of the intubation and RSI.
Continued sedation and analgesia, sometimes with paralysis as well as cardiopulmonary
monitoring, is indicated as long as the patient requires advanced airway support
Etomidate, the most commonly used sedative for RSI in adults, can also be administered
for pediatric RSI.31 The usual dose is 0.3 mg/kg or 20 mg in a 70-kg adult. It often
is used in trauma patients with known or potential bleeding, hypovolemic patients, and
patients with limited cardiac reserve, because it does not have significant cardiovascular
effects. Etomidate also decreases ICP and the cerebral metabolic rate, which
suggests that it may have a neuroprotective effect. These features are why some clinicians
consider it the sedative of choice in a patient who has multiple trauma with
both a head injury and hemorrhage or shock.
Etomidate does inhibit 11-b-hydroxylase, an enzyme necessary for adrenal steroid
production.35 Transient adrenal suppression has been noted after a single dose of etomidate,
although this is probably not clinically significant.36 Some data indicate that
etomidate has a negative impact on patient outcome in critically ill patients with sepsis
and septic shock.37–39 This has led to the suggestion that a corticosteroid be coadministered
when etomidate is given for RSI.38 Although either dexamethasone (0.1 mg/kg)
or hydrocortisone (1–2 mg/kg) may be given, dexamethasone often is chosen because
it does not interfere with the adrenocorticotropin hormone (ACTH) stimulation test,
which may be needed to later test for adrenal insufficiency. In any case, infusions
of etomidate for continued postintubation sedation are contraindicated. Myoclonus is another side effect of etomidate that may interfere with intubation if
a paralytic is not used,40 although this is not the situation with RSI in which a sedative
and paralytic generally are coadministered in quick succession.
Thiopental is the most commonly used barbiturate for pediatric RSI6 and may be the
most commonly used barbiturate for anesthesia induction.41 However, it used is less.
Thiopental decreases both cerebral blood flow and
the metabolic demands of the brain, which makes it an ideal sedative agent in patients
with known increased ICP or patients with head injury who are hemodynamically stable.
Thiopental has negative cardiovascular effects: myocardial depression and peripheral
vasodilatation. Thus, hypotension with associated hypoperfusion can occur
in patients who are hypovolemic or have myocardial depression. Generally, when hypotension
occurs, there is a compensatory baroreceptor mediated reflex tachycardia.
Unfortunately, patients who are hypovolemic or in shock or who are already tachycardic
may not be capable of further compensatory heart rate increases and can experience
a drop in blood pressure with thiopental administration.
Thiopental has some respiratory side effects. It has a dose- and rate-related (eg,
high dose, rapid administration) respiratory depression of the central nervous system
(CNS) that can cause apnea, especially in head injured or hypovolemic patients. With
‘‘light’’ anesthesia, several untoward effects may occur, especially during airway manipulation:
catecholamine release causing systemic or intracranial hypertension, laryngospasm,
cough, and bronchospasm, especially in asthmatic patients.41 To
mitigate or avoid these negative effects, it has been recommended to coadminister
an analgesic (such as fentanyl) especially in head-injured patients.
Ketamine, a dissociative anesthetic, exerts its effects by interrupting the connection
between the thalamo-neocortical tracts and the limbic system. Unlike all the other
sedatives, it has an additional advantage in that it also has analgesic properties.  Ketamine also causes an increase in ICP by both an increase in systemic blood
pressure and cerebral vasodilatation and, therefore, is contraindicated in patients
with ICP, an intracerebral hemorrhage, an intracranial mass, or head trauma; although
a recent study has challenged this contraindication.42 This French study compared the
cerebral hemodynamics of ketamine combined with midazolam and found no significant
difference in ICP or cerebral perfusion pressure when compared with midazolamsufentanil.
Ketamine is probably the sedative of choice for asthmatic patients for many reasons.
Ketamine, through the release of endogenous catecholamines, relieves bronchospasm
by dilating bronchial smooth muscle and stimulating the pulmonary
b receptors. Ketamine increases tracheobronchial/oropharyngeal secretions. Fortunately, pretreatment with atropine (preferred for RSI) or glycopyrollate (preferred
for sedation) prevents excess secretions.27,44 The dose of atropine for RSI is
0.01 to 0.02 mg/kg intravenously with a minimum of 0.1 mg and a maximum of 0.5
to 1.0 mg. Glycopyrollate is the antimuscarinic drug of choice for procedural
sedation because it has a greater antisialagogue effect and fewer side effects (less
tachycardia, fewer dysrhythmias, and no CNS side effects).44 In addition, atropine
crosses the blood–brain barrier (glycopyrollate does not so it has no CNS side effects)
and may increase the incidence of emergence reactions.
The main disadvantage of the benzodiazepines
is that they can cause respiratory depression and apnea. Other uncommon
side effects are paradoxical agitation, vomiting, coughing, and hiccups.
Propofol is an ultra–short-acting sedative hypnotic agent. It has no analgesic effects,
and its amnestic effects are variable. The advantages of propofol are its very quick. onset and short duration. It also has antiemetic properties, can be used in malignant
hypothermia patients. Propofol also has negative cardiovascular
effects so it should be used with caution in patients with volume depletion, hypotension,
or cardiovascular disease.

The nicotinic receptor, a protein particle located on the postsynaptic myocyte membrane
has two parts: a binding component and an ionophore component. The binding
component projects outward from the postsynaptic myocyte membrane into the synaptic
space where it binds the neurotransmitter Ach. The ionosphere component extends
through the postsynaptic neural membrane to the interior of the postsynaptic
membrane. The ionosphere may serve as an ion channel that permits the movement
of ions (in this case primarily sodium ions, as well as other ions) through the membrane.
Acetylcholine (Ach), the neurotransmitter at cholinergic synapses, is released from the
ending of preganglionic and postganglionic parasympathetic nerves and preganglionic
sympathetic nerves.
Ach then diffuses across the synaptic cleft to the motor endplate. Attachment of Ach
to the nicotinic receptors on the skeletal muscle leads to a conformational change in
the nicotinic receptor. This altered protein molecule on the nicotinic skeletal muscle
receptor increases the permeability of the skeletal myocyte cell to various ions (sodium,
potassium, chloride, and calcium) with an influx of sodium into the skeletal myocyte
(see Fig. 4). This produces a large positive potential charge within the skeletal myocyte, referred to as the ‘‘end plate potential.’’ The end plate potential creates an
action potential that travels along the skeletal myocyte membrane causing muscle
contraction. The release of Ach from the nicotinic receptor on the skeletal myocyte ends depolarization.
Ach can either diffuse back into the nerve ending or be broken down by the
acetylcholinesterase enzyme into choline and acetic acid (see Fig. 5). Under normal
circumstances, large amounts of the enzyme acetylcholinesterase are found in the
synaptic space.
Neuromuscular blocking agents (NMBs) are substances that paralyze skeletal
muscles by blocking nerve impulse transmission at the neuromuscular or myoneural
(muscle-nerve) junction.
There are several critical factors to remember with RSI. First, a sedative is coadministered
with the NMB. Patients given an NMB may be aware of their environment, including
painful stimuli, even though they are unable to respond. Failure to sedate the
patient allows the possibility of negative physiologic responses to airway manipulation
such as increased ICP, hypertension, and tachycardia. In addition, the patient may be
aware of and remember the intubation, which is considered inhumane. Concomitant
sedative use limits or helps avoid these adverse physiologic responses to airway manipulation
and may even result in a better view of the airway during laryngoscopy.
However, whenever an NMB is used, the physician must be prepared for a difficult
or failed airway with the possibility that a surgical airway may be necessary if the patient
cannot be oxygenated or ventilated adequately with a bag-valve mask or extraglottic
device. Assessment of the airway, especially if there is the potential for
a difficult or failed airway, should be done before administering an NMB.
NMBs are depolarizing or nondepolarizing. Depolarizing agents mimic the action of
Ach. They case a sustained depolarization of the neuromuscular junction, which prevents
muscle contraction. Nondepolarizing agents work by competitive inhibition to
block Ach’s action at the neuromuscular junction to prevent depolarization.
This nonspecific action at sites throughout the body, eg, nicotinic (ganglionic)
and muscarinic autonomic sites, not just at the neuromuscular junction, helps explain
some of their side effects.
Sch is the prototype of the depolarizing agents. Because its chemical structure (eg,
quaternary ammonium compound) is similar to that of Ach, it binds to the acetylcholine
receptor (AchR) on the motor end plate and depolarizes the postjunctional neuromuscular
membrane, resulting in continuous stimulation of the motor end plate AchRs. The
neuromuscular block/motor paralysis is terminated when the NMB (eg, Sch) unbinds
from the AchR and diffuses back into the circulation where it is hydrolyzed by plasma
cholinesterase. Plasma cholinesterase (also referred to as ‘‘pseudocholinesterase’’ or
‘‘butylcholinesterase’’) rapidly hydrolyses Sch to succinylmonocholine (a very weak
NMB) and choline. Sch’s short duration of action is caused by the rapid hydrolysis
by plasma cholinesterase both before Sch reaches and after Sch leaves the neuromuscular
junction, because there is minimal if any pseudocholinesterase at the neuromuscular
junction. Some Ach may diffuse back into the nerve terminal, although the
majority of Ach is hydrolyzed by plasma cholinesterase. Muscle contraction will not reoccur
until the neuromuscular junction returns to the resting state and then is depolarized
again. Transient fasciculations (caused by initial depolarization) are followed by
blockade of neuromuscular transmission with motor paralysis when Sch is given.
The major advantages of Sch are its rapid onset with complete motor paralysis occurring
within 45 to 60 seconds and short duration of action lasting only 6 to 10 minutes
when given in the recommended 1.5-mg/kg intravenous dose. Do not underdose the drug. It
is preferable to overestimate rather than underestimate the dose because an insufficient
dose may make it difficult to intubate if the patient is not adequately paralyzed. The recommended Sch dose in infants (including neonates) is 2 mg/kg
based on their higher volume of distribution,21,47 and some even recommend up to
3 mg/kg in newborns.47 Administer Sch as a rapid bolus followed by a 20 to 30 cc saline
flush to avoid incomplete paralysis. Sch has been given intramuscularly in a 3- to
4-mg/kg dose in a rare life-threatening situation in which there is inability to obtain venous
access. The absolute contraindications to Sch are (1) a history of malignant hyperthermia in the
patient or family and (2) patients at high risk of severe hyperkalemia.
dosing or prolonged use of Sch potentiates its effects at the sympathetic ganglia and
vagal effects. The negative muscarinic effects from vagal stimulation may lead to bradycardia
and hypotension even at recommended doses. This is one reason some experts
recommend atropine pretreatment in infants/small children, anyone with
significant bradycardia, and those receiving multiple doses of Sch.
Malignant hyperthermia is a rare genetic myopathetic disorder precipitated by multiple
drugs, especially certain inhalational anesthetics (such as halothane, sevoflurane, desiflurane,
isoflurane) and Sch. It is thought to be caused by an abnormal ryanodine receptor
causing marked leakage of calcium from the sarcoplasmic reticulum of skeletal
muscle cells resulting in extremely high intracellular calcium levels.
Even in ‘‘normal’’ patients, Sch may increase the serum potassium up to 0.5 mEq/L
because of depolarization of the myocytes (skeletal muscle cells). Generally, the rise
has no clinical significance except in patients with a predisposition to hyperkalemia,
such as a patient with rhabdomyolysis or patients with chronic skeletal muscle disease
in whom there is ‘‘up-regulation’’ from increased sensitization of extrajunctional AchR.
so the risk of life-threatening hyperkalemia
does not start until days (usually 3–5 days) after the injury or illness onset.
Although the longstanding tenet has been to avoid Sch in patients in chronic renal
failure who have normokalemia, there is no supportive evidence for this.
Its safe in patients with Increased intracranial pressure and intraocular pressure. Fasciculations are involuntary, unsynchronized muscle contractions. They are caused
by the depolarization of Ach receptors.
Nondepolarizing (ND) NMBs competitively block Ach transmission at the postjunctional
cholinergic nicotinic receptors. Unlike Sch, which causes a conformational change
in the AchR receptor resulting in depolarizination of the neuromuscular junction, the
nondepolarizing NMB prevents Ach from access to the nicotinic receptor, thereby preventing
muscle contraction. Fasciculations do not occur with the ND-NMBs.
Currently, the only ultra short NMB available in the United States is the depolarizing
NMB, Sch. However, doubling the dose of rocuronium from 0.6 mg/kg to 1.2
mg/kg shortens the onset of complete neuromuscular blockade from about 1.5 minutes
(mean, 89 seconds) to 1 minute (mean, 55 seconds).50 If Sch cannot be used
and intubation in less than 90 seconds is needed, then the higher doses of the NDNMB
can be used.
The ND-NMBs are used: 1) for muscle relaxation if Sch is contraindicated or unavailable,
2) to maintain postintubation paralysis (remember that repeated doses of Sch
should be avoided, if possible), and 3) as a pretreatment agent to lessen or eliminate
the fasciculations and their side effects (eg, myalgias and increased IOP, ICP, intragastric
pressure [IGP]) associated with Sch use.
Short-acting ND-NMBs include rapacuronium
and mivacurium; intermediate acting include vecuronium, rocuronium,
atracurium, and cisatracurium; and long-acting include pancuronium, pipecuronium,
d-tubocurarine, metacurine, doxacurium, alcuronium, and gallamine.
A Cochrane meta-analysis concluded ‘‘succinylcholine
created superior intubation conditions to rocuronium when comparing
both excellent and clinically acceptable intubating conditions.
In clinical practice, the ND-NMB is generally administered 2 minutes before giving
the intubating dose of Sch. Giving ND-NMB increases the muscle’s resistance
to Sch’s action such that increasing the Sch dose by 50% is recommended. for the emergent intubation in the ED
is the extra time (about 2 or more minutes) added to the procedure before intubation
occurs. Some clinicians also use fasciculations as a clue to when neuromuscular
blockade has occurred, and conditions are ready for ET tube placement.
A drug familiar to emergency medicine, lidocaine, can be used as an alternative to
ND-NMB for priming before Sch administration. Lidocaine is effective in minimizing or
preventing the fasciculations with their side effects that occur after Sch administration.
The dose is 1.5 mg/kg of lidocaine.
‘‘Facilitated intubation’’ refers to the use of a sedative only (without a paralytic) to pharmacologically
assist with intubation. Facilitated intubation, also referred to as ‘‘pharmacologically
assisted intubation,’’ has been recommended by some clinicians in
specific circumstances because it does not involve neuromuscular blockade. Some
advocate the avoidance of a neuromuscular paralysis and the use of sedation alone
(‘‘facilitated intubation’’) in clinical scenarios in which a difficult airway is anticipated.
For facilitated intubation, the most common sedative used has been etomidate, although
midazolam has also bee used.
For ED intubations, the results of the NEAR studies confirm the superiority of RSI
over facilitated intubation.6,34 The successful intubation rate for first attempt was
RSI 5 85%, and sedative only (no NMB) 5 76%. The successful rate for first intubation
was RSI 5 91%, and sedative only (no NMB) 5 88%.34 For pediatric patients, the
first attempt intubation success rates were RSI, 78%; sedative only, 44%; and no
medication. 47%