Tuesday December 25, 2007
Merry Christmas

Monday December 24, 2007

Case: 57 year old female, newly hemodialysis patient, transferred from floor to ICU after she developed seizure at the end of her dialysis session. No significant risk factor could be find otherwise. Nurse reports patient appear irritable and restless before episode and complain of headache, nausea and blurred vision. While resident was called to evaluate as patient also noticed to have muscular twitching and confusion, symptoms progressed and seizure was witnessed.

Answer: Dialysis disequilibrium syndrome.

Dialysis disequilibrium syndrome is common during hemodialysis particularly patient’s first few dialysis sessions. It is characterized by neurologic symptoms of varying severity and actually may lead to herniation and death. The rapid reduction in BUN lowers the plasma osmolality, creating a transient osmotic gradient that promotes water movement into the cells, causing cerebral edema and consequently acute neurologic dysfunction. With better understanding of the process and newer dialysis techniques, severe form of syndrome is now not commonly seen. This not only explains that why our nephrology colleagues start with gentle but frequent sessions but also explains one of the several benefits of mannitol during dialysis.


Read interesting article from University of Calgary, Alberta, Canada : Dialysis Disequilibrium Syndrome: Brain death following hemodialysis for metabolic acidosis and acute renal failure - A case report followed with discussion and different management modalities (Ref.: BMC Nephrol. 2004; 5: 9.)

Sunday December 23, 2007
Paracentesis (Procedure video)

Saturday December 22, 2007
Re. Fentanyl Cough

Fentanyl is probably the most commonly used opioid in ICUs. Fentanyl is associated with coughing in upto 30% of patients. Usually its benign but may become explosive causing discomfort and increased intracranial and intra-ocular pressures. The various mechanisms proposed to explain fentanyl induced cough are inhibition of central sympathetic outflow leading to vagal predominance, histamine release or deformation of the tracheobronchial wall stimulating the irritant receptors.

Treatment is aerosol inhalation of Salbutamol, beclomethasone or sodium chromoglycate if needed.


References: click to get abstract / article

1. Explosive coughing after bolus fentanyl injection. Anesth Analg 2001; 92: 1442–3.
2. Tussive effect of a fentanyl bolus administered through a central venous catheter. Anaesthesia 1990; 45: 18–21.
3. Tussive effect of a fentanyl bolus. Can J Anaesth 1991; 38: 330–4
4. Central vagal control of fentanyl-induced bradycardia during halothane anesthesia. Anesth Analg 1978; 57: 31–6
5. Tracheal constriction by morphine and by fentanyl in man. Anesthesiology 1978; 49: 117–9.
6. Salbutamol, beclomethasone or sodium chromoglycate suppress coughing induced by iv fentanyl Canadian Journal of Anesthesia 50:297-300 (2003)

Friday December 21, 2007



What is the difference between Renagel and Renvela ?

Sevelamer is indicated for the control of serum phosphorus (P) in patients with Chronic Kidney Disease on hemodialysis. Sevelamer controls phosphorus and "Ca x P product" without the concerns of metal accumulation.

Renagel and Renvela are two forms of Sevelamar.

Renagel is Sevelamar Hydrochloride while Renvela is the Sevelamar carbonate. Both tablets are produced by the same company and available in 800 mg forms.

Renvela, being in carbonate form has advantage as acid buffer and reduce the risk of acidosis. Renvela is a a next generation phosphate binder which will eventually replace Renagel (sevelamer hydrochloride).

Thursday December 20, 2007
Bedside tip - ECMO and lipid infusion

If you have a patient receiving extracorporeal membrane oxygenation (ECMO), TPN * should be instituted WITHOUT IV lipids. IV lipid emulsion increases the incidence of layering out, agglutination, or clot formation during ECMO. This may result in disruption of normal ECMO blood flow.

* TPN = Total Parenteral Nutrition


Related previous pearls: ECMO, ABGs while patient on ECMO

Important trial to watch: Multicenter CESAR trial - (Conventional ventilation or ECMO for Severe Adult Respiratory Failure - 180 patients) - The first international presentation of the results will be presented at the Society of Critical Care Medicine's 37th Critical Care Congess in Hawaii, February 2008.



References :

1. Comparison of methods for intravenous infusion of fat emulsion during extracorporeal membrane oxygenation . Pharmacotherapy 2005;25(11):1536-1540

Wednesday December 19, 2007
4 Carbapenems


Doripenem is the new agent added to the list of Carbapenems, making the list to grow to 4.

1. Primaxin (imipenem/cilastatin),
2. Meropenem (Merrem),
3. Invanz (ertapenem) and
4. Doripenem (Doribax)

Major points to remember about each carbapenem is

Primaxin is marked by associated neurotoxicity. It may decrease seizure threshold, particularly in renal patients.

Invanz is a very effective broad-spectrum choice against community acquired severe infections but does not cover pseudomonas and acinetobacter. It is now increasingly used as prophylaxis of surgical site infection following elective colorectal surgery, given as single 1-g dose given within 1 hour before surgical incision.

Meropenem is safest in terms of neuro-toxicity and also covers MDR pseudumonas and acinetobacter.

Newly introduced Doripenem is similar in clinical use as meropenem but is highly more effective with lower 50% inhibitory concentrations (MIC50) and 90% inhibitory concentrations (MIC90) for multidrug-resistant strains of mucoid Pseudomonas aeruginosa, nonmucoid P. aeruginosa and Burkholderia cepacia complex. This gives it advantage to be use in cases previously refractory to carbapenem therapy.



References : click to get abstract/article

1. In Vitro Activity of Doripenem (S-4661) against Multidrug-Resistant Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis - Antimicrobial Agents and Chemotherapy, June 2005, p. 2510-2511, Vol. 49, No. 6

2. Doripenem (S-4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluations - Journal of Antimicrobial Chemotherapy 2004 54(1):144-154;

Tuesday December 18, 2007
Thing you may like to know about viagra !

There are recent reports and FDA warning for cases of sudden decreases or loss of hearing following the use of PDE5 inhibitors, Viagra, Levitra, and Cialis (erectile dysfunction) and Revatio (pulmonary arterial hypertension). Hearing loss is mostly unilateral, may be sudden and may accompanied by tinnitus, vertigo and dizziness. Also, there are concerns that hearing loss may persist for long.

As PDE5 inhibitors are getting more commonly used in ICUs for pulmonary HTN, it may be of importance to be aware of this side effect.


Reference:

Sildenafil (marketed as Viagra and Revatio) Vardenafil (marketed as Levitra) Tadalafil (marketed as Cialis) - FDA

Monday December 17, 2007
Re. Purple Glove Syndrome

Here are few responses re. our pearl from 2 days back, Phenytoin induced Purple glove syndrome


1) "I've given a lot of phenytoin over the years and I've never seen this. Neither have most of the people I know. The Mayo epilepsy group are are very good, and I don't discount what they have written (upto 5.9% *) but it seems unusual that no one else seems to see it more often than once in a blue moon. I have seen bad extravasations, which is more likely the cause of the problem. And, the crystallization of phenytoin in microvessels makes no sense as an explanation of a local complication for a drug being given intravenously.

Disclaimer: Much of the phenytoin I've given has been through a central line, where this wouldn't be an issue ".

* (Ref. # 1 in said pearl: Incidence and clinical consequences of purple glove syndrome in patients receiving intravenous phenytoin, Neurology, 1998:51:1034-1039),


Thomas P. Bleck MD FCCM
Ruggles Chairman of Neurology, Evanston Northwestern Healthcare;
Vice Chair for Academic Programs, Department of Neurology, and
Professor of Neurology, Neurological Surgery, and Medicine,
Northwestern University Feinberg School of Medicine
Founding Past President, The Neurocritical Care Society(http://www.neurocriticalcare.org)



2) "It must be once in a blue moon, as I have witnessed this only twice during my practice. Please check out the link below

Photo Quiz - Distal Upper Extremity Edema and Discoloration

Surindra J. Singh, M.D., Intensivist, VAMC, Salem, VA 24153 Surindra.Singh@va.gov




3) "This is well described with thiopentone and other drugs which is worsened by inadvertent intra-arterial injection.(Intravenous injection is followed by secondary arterial spasm) Things to do is heparinization. IV /intrarterial lignocaine and a symptathetic blockade by an axillary block to relieve reflex vsasopspasm. The one thing NOT to do is remove the intrarterial line if this happens due to inadvertent intrarterial injection. immediately inject any vasodilator like nitroglycerine or nitroprusside, heparin and papaverine diluted in blood through the line. If the line is removed intrarterial accesss will be lost. Many a time so called intravenous access is actually due to an intrarterial placement of a variant branch of the radial arterywhich being a smaller brach does not give a very good arterial flashback.This is well described in the 1960's by Bailey in his textbook of emergency surgery. A point well to be learnt from a historical textbook that has a lot of home truths which are true even today".

"Prasanna Simha M" , prasannasimha@gmail.com

Sunday December 16, 2007


Case: 47 year old male of Indian sub-continent origin admitted to ICU with status epilepticus. Patient has recently been started on TB prophylaxis medicine at his new work place. What is your probable diagnosis and what would be the treatment?



Answer: Isoniazid (INH) induced seizures.

Isoniazid (INH) induced seizures is unique in the sense that it is usually refractory to standard anticonvulsant therapy. Even dose as low as as 1.5 g can be neurologically toxic.

INH induced seizure requires administration of a specific antidote, pyridoxine (B-6), with dose of 5 gram in IV form. Dose can be repeated 2 to 3 times if needed.




Reference: click to get article

1. INH Induced Status Epilepticus: Response to Pyridoxine - [Indian J Chest Dis Allied Sci 2006; 48: 205-206].

Saturday December 15, 2007
Wernicke's Encephalopathy in ICU

Q: Can Wernicke's Encephalopathy be iatrogenic in ICU ?

A: Yes, it can be precipitated in any patient by glucose (like D-5, D-10 or D-50) administration who is thiamine deficient. It is not limited to alcoholics and can happen in any nutritionally deficient patient. It is always a good idea to add thiamine in D-5 drip in patients who are at risk of Wernicke's Encephalopathy. Disorder was described about 25 years ago by Carl Wernicke as a triad of

• acute mental confusion
• ataxia
• opthalmoplegia

Read a case of Wernicke's encephalopathy. in a non-alcoholic patient with MRI findings here ( Ref.: The New England Journal of Medicine, Kaineg and Hudgins 352 (19): e18, May 12, 2005 )

Also see full review article Wernicke's encephalopathy at emedicine.com


Refrences: click to get abstract/article

1. Incidence and clinical consequences of purple glove syndrome in patients receiving intravenous phenytoin, Neurology, 1998:51:1034-1039.
2. A prospective study of the purple glove syndrome , Epilepsia, 2001:42(9):1156-1159.
3. Purple glove syndrome : A complication of intravenous phenytoin, J. of Neuroscience Nursing, 1992:24(8):340-345.
4. Purple glove syndrome: a complication of intravenous phenytoin. - J Neurosci Nurs.1992 Dec;24(6):340-5

Friday December 14, 2007
Phenytoin induced Purple glove syndrome


Purple glove syndrome also known as PGS is a progressive distal limb edema, discoloration, and pain after peripheral administration of phenytoin. If unrecognised, it may lead to severe skin necrosis, limb ischemia and to compartment syndromes. It is a fairly unknown and under diagnosed complication with IV Phenytoin and reported in upto 5% of cases. It is mostly overlooked due to reflexly made diagnosis of cellulitis at IV site.


Mechanism of action: 2 probable mechanisms has been described.


1. Phenytoin is poorly soluble at neutral PH. Solutions like sodium hydroxide, propylene glycol and ethanol are added to enhance solubility by increasing PH. Highly alkaline solution may induce vasoconstriction and thrombosis in vessels – may allow leakage into interstitial space.


2. Mixing of alkaline phenytoin solution with blood induce precip. of phenytoin crystals, leading to obstruction of micro vessels causing ischemia and also may induce leakage.


Treatment : is mostly supportive with elevation of limb, compression, dry, gentle heat, galvanic stimulation and in severe cases fasciotomy, skin grafting or amputation.



Refrences: click to get abstract/article

1. Incidence and clinical consequences of purple glove syndrome in patients receiving intravenous phenytoin, Neurology, 1998:51:1034-1039.
2. A prospective study of the purple glove syndrome , Epilepsia, 2001:42(9):1156-1159.
3. Purple glove syndrome : A complication of intravenous phenytoin, J. of Neuroscience Nursing, 1992:24(8):340-345.
4. Purple glove syndrome: a complication of intravenous phenytoin. - J Neurosci Nurs.1992 Dec;24(6):340-5

Thursday December 13, 2007
Value of Troponins in Acute Pulmonary Embolism

Troponin level is still struggling to find its place in non-cardiac diseases. A meta-analysis is performed in Italy to see prognostic value of troponins in acute pulmonary embolism for short-term death and adverse outcome events (composite of death and any of the following: shock, need for thrombolysis, endotracheal intubation, catecholamine infusion, cardiopulmonary resuscitation, or recurrent pulmonary embolism).

Data of 20 studies, spread from January 1998 to November 2006 (including 1985 patients) were included in the analysis.

Results:

• 122 of 618 patients with elevated troponin levels died (19.7%) compared with 51 of 1367 with normal troponin levels (3.7%).
• Elevated troponin levels were significantly associated with short-term mortality, with death resulting from pulmonary embolism and with adverse outcome events
• Elevated troponin levels were associated with a high mortality in the subgroup of hemodynamically stable patients.

Study concluded that — Elevated troponin levels identify patients with acute pulmonary embolism at high risk of short-term death and adverse outcome events.


Reference: Click to get abstract/article

Prognostic Value of Troponins in Acute Pulmonary Embolism - Circulation. 2007;116:427-433.)

Wednesday December 12, 2007
Clonidine Toxicity

Q; The treatment of clonidine toxicity is mostly supportive. Which antidote has shown (only anecdotal reports) to reverse altered mental status and associated hypotension with clonidine toxicity ?

A; Naloxone (Narcan).

There are few case reports in literature describing naloxone to improve the altered mental status associated with clonidine toxicity. It also reverses hypotension but may induce severe hypertension while reversing clonidine effect and should be use with caution. Dose should be initiated from 0.2 IV and can be titrated upto 2 mg IV. Doses upto 5-10 mg have been reported but again caution should be exercise.

Another antidote described in literature for clonidine toxicity is yohimbine. (Yohimbine is a central alpha2-adrenergic antagonist). The dose is a single 5.4 mg tablet via enteral route.

Dopamine is the choice of vasopressor in clonidine induced hypotension after IVF boluses. And, atrpoine to counteract bradycardia associted with it.


References: click to get abstract / article

1. Reversal of clonidine toxicity by naloxone - Ann Emerg Med. 1986 Oct;15(10):1229-31.
2. Clonidine toxicity revisited - J Toxicol Clin Toxicol. 2002;40(2):145-55.
3. Yohimbine as an antidote for clonidine overdose - Am J Emerg Med.1996 Nov;14(7):678-80.
4. Clonidine overdose: report of six cases and review of the literature - Ann Emerg Med. 1981 Feb;10(2):107-12.
5. Toxicity, Clonidine - emedicine.com

Tuesday December 11, 2007
Why PO Demerol is not a good idea !!

Overall, demerol (meperidine) is falling out of favor and has been referred by many as 'demon' due to neurotoxicity of its metabolite normeperidine. Fortunately PO (by mouth) demerol is not as popular as IV but it should be avoided at all. PO demerol is way more dangerous than IV demerol. 50% of PO demerol get metabolized first pass via liver and give high level of normeperidine in blood which has long half life of 15-30 hours even with normal kidney function and may accumulate to cause tremors, myoclonus, hallucinations and seizure. Hemodialysis has been described to help in normeperidine toxicity 1.

See nice review at medscape.com - free registration required: Meperidine is Alive and Well in the New Millennium: Evaluation of Meperidine Usage Patterns and Frequency of Adverse Drug Reactions (Dr. Seifert and Dr. Kennedy, Ref: Pharmacotherapy 24(6):776-783, 2004)


Reference: click to get abstract

Successful treatment of normeperidine neurotoxicity by hemodialysis - Am J Kidney Dis. 2000 Jan;35(1):146-9.

Monday December 10, 2007
How many attempts to intubate?


Its hard to give up procedure if you are failing it !! For intubation, ASA (American Society of Anesthesiologists) recommends to limit laryngoscopic attempts to three. Dr. Thomas C. Mort from Hartford Hospital, CT entered 2833 Critically-ill patients, suffering from cardiovascular, pulmonary, metabolic, neurologic, or trauma-related deterioration into an emergency intubation quality improvement database. Data confirmed that the number of laryngoscopic attempts were directly proportional with the incidence of airway and hemodynamic adverse events (more than 2 attempts).

• incidence of hypoxemia went from 11.8% to 70%,
• incidence of regurgitation of gastric contents went from 1.9% to 22%,
• incidence of aspiration of gastric contents went from 0.8% to 13%,
• incidence of bradycardia went from 1.6% to 21%, and
• incidence of cardiac arrest went from 0.7% to 11%

Call for help !! and remember, to limit intubation attempts to 3, unless untill you are trained to deal with 'difficult intubations'.





References: click to get abstract/article

1. Emergency tracheal intubation: complications associated with repeated laryngoscopic attempts - Anesth Analg 2004;99:607-613

Sunday, December 9, 2007


Q: what is "cryo reduced plasma"?

A; Yesterday we learned that: one unit of cryoprecipitate is derived from one unit of fresh frozen plasma (FFP). Left over FFP, after removal of cryoprecipitate is called supernatant plasma or CRYO-REDUCED PLASMA.


Clinical Significance: Cryo-reduced plasma is used as a treatment in plasmapheresis for TTP, not responding to regular plasma exchange with FFP. Some physicians even use it as first line for plasmapheresis/Therapeutic Plasma Exchange (TPE) for a patient with Thrombotic Thrombocytopenic Purpura (TTP).

Saturday December 8, 2007
Ethanol drip in Ethylene Glycol

Q; How you write Ethanol drip in Ethylene Glycol poisoning assuming you don't have Fomepizole or Dialysis available ?

A: Ethylene Glycol poisoning is common and can have bleak outcomes. Intensivists should be aware of all the possible interventions available. Antidotal therapy is based on preventing the alcohol dehydrogenase enzyme from metabolizing ethylene glycol into toxic byproducts. In case Fomepizole or Dialysis is not available, Ethanol will competitively inhibit alcohol dehydrogenase. But the serum ethanol level must be monitored frequently.Therapeutic ethanol is administered in a bolus followed by a continuous infusion.

Initially, 7.5 to 10 mL/Kg of 10% ethanol, in D5W, is administered over 30 minutes. Then, a continuous infusion of 1 to 2 mL/Kg/hr of 10% ethanol is infused until the patient has eliminated all of the EG from his serum.

It is important to keep the serum ethanol level at 100 to 150 mg/dL so as to completely inhibit the alcohol dehydrogenase enzyme.

Friday December 7, 2007
Resistant (uncontrolled) / Life-threatening diffuse alveolar hemorrhage

Diffuse alveolar hemorrhage remained a condition with high mortality. Usual treatment is high dose IV methylprednisolone (1g/day) for three to five days and in more severe cases to add IV cyclophosphamide (cyclophosphamide has a delayed effect, but may provide synergistic action with steroid). Plasmapheresis has been described to be effective particularly in diffuse alveolar hemorrhage associated with Goodpasture syndrome.But what if bleeding is non-stop and life-threatening ?

Answer is off label use of activated Factor VII (Novoseven). In 3 cases reported from University of North Carolina at Chapel Hill - bleeding stops and oxygenation improved within minutes 1.


Reference: click to get abstract

Successful Treatment of Diffuse Alveolar Hemorrhage with Activated Factor VII - annals, 16 March 2004 Volume 140 Issue 6 Pages 493-494

Thursday December 6, 2007


Q; What is the re-intubation rate in your ICU ?

A; Re-intubation rates have been reported in literature anywhere from 4% - 20% but most of the experts agree that as far as its less than 15%, you are in normal / safe zone. Ideal would be less than or equal to 5%. Other way is to keep track of reintubation rate and making sure that it is not increasing in your ICU.

Related links:

HOW TO ESTABLISH A VENTILATOR WEANING PROTOCOL , Gregory P. Marelich, MD - thoracic.org

When to wean from a ventilator: An evidence-based strategy, Ref: CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 70, NUMBER 5 MAY 2003 page 389


Related previous pearls:

• Nasal cannula vs Face mask after extubation ,
• Spontaneous Breathing Trial (SBT) - how long - 30 minutes or 120 minutes?,
• Bedside tip ! - Tracheal Tube Tolerance
• IV steroid to reduces postextubation stridor

Wednesday December 5, 2007

Q; How much intavenous albumin should be given to patient while removing ascitic fluid via paracentesis?

A; Per 2004 guidelines published in Hepatology 2004 Mar;39(3):841-56, for management of adult patients with ascites due to cirrhosis by Practice Guidelines Committee, American Association for the Study of Liver Diseases (AASLD),

"Post-paracentesis albumin infusion may not be necessary for a single paracentesis of less than 4 to 5 L. For large-volume paracenteses, an albumin infusion of 8 to 10 g per liter of fluid removed can be considered".

(Grade II-2 evidence - Cohort or case-control analytic studies).

Read full guidelines here

Tuesday December 4, 2007
Mix for Norepinepherine

Do you know that.....NOREPINEPHRINE (LEVOPHED) is less stable in normal saline (loose its potency from oxidation). It is preferred to be mix in dextrose as the dextrose protects against oxidation of the norepinephrine and keep it active and stable.

Monday December 3, 2007
What Dig. level makes you happy ?

Digoxin is known to provid reduction in hospitalizations among patients with heart failure and depressed left ventricular systolic function without improving mortality (DIG trial -The Digitalis Investigation Group trial) 1. Very interesting work published in JAMA about 3 years ago (about 3800 patients) as a followup of above trial - looking into mortality association with different Digoxin level 2 . What they found:

* SDC = serum digoxin concentration
* Patients were divided into 3 groups based on SDC at 1 month

• Patients with SDCs of 0.5 to 0.8 ng/mL had a 6.3% lower mortality rate compared with patients receiving placebo.
• No reduction in mortality among patients with SDCs of 0.9 to 1.1 ng/mL,

And

• Patients with SDCs of 1.2 ng/mL and higher had an 11.8% higher absolute mortality rate than patients receiving placebo.

Study suggested that the effectiveness of digoxin therapy in men with heart failure and a left ventricular ejection fraction of 45% or less may be optimized in the SDC range of 0.5 to 0.8 ng/mL.


Read interesting article: DIGOXIN DELUSIONS (from ucsf.edu)



References: Click to get abstract

1. The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure, The Digitalis Investigation Group - NEJM, Vol 336, Feb 20, 1997, number 8

2. Association of Serum Digoxin Concentration and Outcomes in Patients With Heart Failure -JAMA. 2003;289:871-878.

Sunday December 2, 2007


Q; Which condition may mimic pseudo-atrial flutter on EKG and monitor?

A; Parkinsonian tremor (first reported about 40 years ago 1 and later on many other reports confirmed it). Recently in, Mayo Clinic Proceedings, a case has been reported of pseudo atrial flutter with use of portable CD player by patient. 2


References:

1. MUSCLE-TREMOR ARTIFACT DUE TO PARKINSON'S SYNDROME. IT STIMULATED ATRIAL FLUTTER AND DISAPPEARED DURING SLEEP - Postgrad Med. 1965 Jun;37:718-20.

2. Atrial flutter simulated by a portable CD player - mayo clinic proceedings - march 2006,82(3), Page 383 -pdf file

Saturday December 1, 2007
Zolpidem-Induced Delirium

Relatively Zolpidem (Ambien) is a safe medicine and recently has been the drug of choice in critical care units to induce sleep. But it is important to be aware of reported cases of Ambien related psychosis, delirium and mania.

Atleast one case is reported with visual perception distortion after a single dose of zolpidem.

One way to combat the problem is to decrease the prescribing dose particularly in elderly population and in hypoalbuminemia (5 mg instead of 10 mg). Also, female population has been reported to have more plasma level with same dose. Also note that Zolpidem metabolized through liver so it may be necessary to decrease the dose in liver insufficiency.

Related previous pearls: SEROTONIN SYNDROME



References: click to get abstract / article

1. Delirium associated with zolpidem - The Annals of Pharmacotherapy: Vol. 35, No. 12, pp. 1562-1564
2. Zolpidem-Induced Delirium With Mania in an Elderly Woman - Psychosomatics 45:88-89, February 2004
3. Zolpidem-induced agitation and disorganization. - Gen Hosp Psychiatry. 1996 Nov;18(6):452-3. (pubmed)
4. Zolpidem-induced psychosis. - Ann Clin Psychiatry.1996 Jun;8(2):89-91. (pubmed)
5. Clinical pharmacokinetics of zolpidem in various physiological and pathological conditions, in Imidazopyridines in Sleep Disorders. Edited by Sauvanet JP, Langer SZ, Morselli PL. New York, Raven Press, 1988, pp 155–163
6. Zolpidem-Induced Distortion in Visual Perception - The Annals of Pharmacotherapy: Vol. 37, No. 5, pp. 683-686