Friday June 30, 2006
Double the dose of mucomyst ?

A noteworthy study came out yesterday in The New England Journal of Medicine1 regarding protective effect of N-Acetylcysteine in Contrast-Induced Nephropathy in primary angioplasty. When the cumulative dose of N-Acetylcysteine was doubled from 3000 mg (a 600mg IV bolus before angioplasty followed by 600 mg orally twice daily for the 48 hours after angioplasty) to 6000 mg (a 1200 mg IV bolus followed by 1200 mg orally twice daily for the 48 hours after intervention), it showed

• significant decrease in increase of serum creatinine concentration (15 percent vs 8 percent)
  
• overall decrease in in-hospital mortality in patients with contrast induced nephropathy (4 percent vs 3 percent).
  
• When the combined end point of death, acute renal failure requiring temporary renal replacement therapy, or the need for ventilator during the acute phase of myocardial infarction was considered, the rate was 7% in the standard dose group, and 5% in the high dose group.

In study there were 3 groups - placebo, standard dose and double dose.

It appears that, the benefit of high-dose N-acetylcysteine is greater in patients receiving a larger or more than regular volume of contrast.

Conclusion: N-acetylcysteine reduced the severity of contrast medium induced nephropathy in patients with acute myocardial infarction treated with primary angioplasty. The effect appears to be dose dependent and is accompanied by a significantly improved in-hospital outcome.

Related previous pearls:
Contrast induced Nephropathy and
Preventing contrast-Induced Nephropathy

Reference: Click to get article/abstract
1. N-Acetylcysteine and Contrast-Induced Nephropathy in Primary Angioplasty - Volume 354:2773-2782, Number 26, June 29 2006
2. Contrast Nephropathy Prevention With N-Acetylcysteine in Acute Myocardial Infarction - clinicaltrials.gov

Thursday June 29, 2006
ICU Index Spider Diagram

The Society of Critical Care Medicine’s (SCCM) Coalition for Critical Care Excellence (CCCE) has developed The ICU Index™ (click to get more details) as a measurement tool that can be used at the individual ICU level to baseline a series of performance variables and then track progress. It look into 16 important measures and can either be approached in a regular bar chart form or as a spider diagram.

Goal is to move the said measure as much as possible inside the spider to central target. Comparing spider diagrams every few months can tell improvements in ICU in just one glance. See the diagram above. You may wish to change, add, substract measures like you can track VAP rate, LOS etc as per your local ICU need.

If you would like more information, or would like to participate in the pilot project, please email ICUIndex@sccm.org.

Diagnostic criteria of Delirium

Wednesday June 28, 2006
Diagnostic criteria of Delirium

Q: What are 4 basic criteria to label patient as having Delirium?

A: Per American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders. 4th ed. (DSM-IV), Patient is having delirium if

1. Disturbance of consciousness (eg, reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention.

2. A change in cognition such as memory deficit, disorientation, language disturbance (or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia).

3. The disturbance develops over a short period of time (usually hours) and tends to fluctuate during the course of the day.

4. Disturbance caused by a general medical condition or substance intoxication or medication use.

Related website:

www.icudelirium.org (must see for intensivists)

Related previous pearls:
Zolpidem-Induced Delirium ,
SEROTONIN SYNDROME ,
Amiodarone Neurotoxicity

References: click to get abstract/article

1. An Empirical Study of Different Diagnostic Criteria for Delirium Among Elderly Medical Inpatients - J Neuropsychiatry Clin Neurosci 15:200-207, May 2003
2. Delirium in Elderly Patients - Focus 3:320-332 (2005)
3. Delirium in Older Persons - N. Engl. J. Med., March 16, 2006; 354(11): 1157 - 1165
4. Delirium - emedicine.com
5. Delirium - American Family Physician® Vol. 67/No. 5 (March 1, 2003)

Tuesday June 27, 2006
We will need more intensivists !!

Currently in USA, only 37% of critically ill patients are cared for by intensivists and an estimated 360,000 deaths occur each year in ICUs not managed by intensivists. In 2003, the US Senate asked Health Resources and Services Administration (HRSA) to work with the American College of Chest Physicians (ACCP) to update critical care workforce models in order to more accurately assess the adequacy of supply for critical care physicians. In the newly released US Department of Health and Human Services Report to Congress: The Critical Care Workforce: A Study of the Supply and Demand for Critical Care Physicians, it has been predicted that the demand for critical care services will increase rapidly, while the intensivist supply would not be able to care for a greater proportion of critically ill patients. The shortage is will be exacerbated by the year 2020 due to the aging population and the increased utilization of intensivists.

By 2020, the demand for intensivists would likely increase by 129 percent above the current supply.

Some Suggestions include:

• Increase role of eICU
• Possible rationing of critical care services or regionalization of ICU services like trauma system
• Restructuring current Medicare reimbursement system
• Expanding National Health Services Corps and J-1 waiver program
• Only deserving patients getting admission to ICU
• Decreasing care for know futile outcomes by more public/physician education
  

Read full report: HRSA Report to Congress. The Critical Care Workforce: A Study of the Supply and Demand for Critical Care Physicians

Monday June 26, 2006
Thrombelastography - TEG

TEG was first introduced about 60 years ago by Hartert . TEG monitors hemostasis as a whole dynamic process and measures the viscoelastic properties of blood. The strength of a clot is graphically represented over time in a cigar shape figure. With little practice, just a glance at shape and size of cigar, it provides clue to underlying disease process. It is an underutilized tool in ICU. See picture for self explanation:


Read review on Thromboelastography/thromboelastometry here (pdf file) (ref: Clin. Lab. Haem. 2005, 27, 81–90)

Sunday June 25, 2006
Introducing iCritical Care Podcasts

www.sccm.org/podcast


iCritical Care Podcasts from Society of Critical Care Medicine is a kind of radio which you can listen on your home computer, or your portable media player (iPod and others). The iCritical Care Podcast is a novel way for you to keep up-to-date with the latest in Critical Care. Site get frequently updated with talks on recent breakthrough articles carrying interviews with authors of these articles as well as talks on non-academic but critical care related issues. So far upto 34 talks have been added including but not limited to:

• Lorazepam vs. Propofol
• Catheter-Related Bloodstream Infections
• Prophylactic Antimicrobial Use in the ICU
• Hospital Mortality Assessment
• Rationing in the ICU
• Morbid Obesity and the Surgical Critical Patient
• Dopamine's Influence on the Outcome of Shock
• Defining and Treating Abdominal Compartment Syndrome
• Early Indicators of Sepsis Survival
• Getting Our ICU Language Straight
• Critical Care Pharmacists
• Implementing the Surviving Sepsis Campaign
  

Host is Richard H. Savel, MD, Associate Director, Surgical Intensive Care Unit at Maimonides Medical Center, Brooklyn, NY, and Assistant Professor of Medicine at Mt. Sinai School of Medicine, NY.

Again site is www.sccm.org/podcast

Related previous themes:
Introducing Resident ICU Course and
PACT - Critical Care distant learning course

fenoldopam

Saturday June 24, 2006

Case: 39 year old male admitted with hypertensive emergency after he ran out of his prescriptions. "ED Doc" started patient on IV cardene (nicardipine) drip and resumed patient's home med for BP which consist of Toprol (metoprolol) XL - first dose given in ER. On review of CXR you noticed some pulmonary edema and decide to switch to Fenoldopam to get dual effect of lowering BP as well as dopaminergic effect to resolve pulmonary edema. Patient dropped his BP precipitously and coded.


Probable cause: It is not advisable to start fenoldopam on patients with B-blocker or atleast close caution should be maintained. Concomitant use of beta-blockers in conjunction with fenoldopam may cause life threatening hypotension from beta-blocker's inhibition of the sympathetic reflex response to fenoldopam 1.


Related previous pearl: Renal dose Fenoldopam ?


References: click to get abstract/article1. Corlopam - fda.gov

2. Fenoldopam — A Selective Peripheral Dopamine-Receptor Agonist for the Treatment of Severe Hypertension - Volume 345:1548-1557, Number 21, Nov. 22,2001

Friday June 23, 2006

Case: 24 year old male admitted with left thigh cellulitis and abcess. I and D was performed and cefazolin (ancef) was initiated. Patient did not respond to cefazolin and antibiotic was changed to vancomycin after availability of sensitivity from micro lab. Patient showed marked improvement over next 3 days except patient complaint of new rash on his body which you attributed to "Red man syndrome" and wrote an order to infuse vancomycin slowly and with increase dilution. Next day, as you reached hospital, you were informed by outgoing intensivist that patient deteriorated overnight and required intubation. You were baffled and as you examine the patient, you find extensive dermal exfoliation along with axillary and inguinal lymphadenopathy. On lab, LDH and liver enzymes were markedly elevated and kidney funtion deteriorated from normal to anuria. CBC showed eosinophilia.


Vancomycin-induced Stevens-Johnson syndrome

Stevens-Johnson syndrome is an acute mucocutaneous process characterized by severe exfoliative dermatitis and mucosal involvement of the gastrointestinal tract and conjunctiva. Pathogenesis is unclear, but an immunological mechanism, probably cell-mediated, has been suggested. Clinical diagnosis of Stevens-Johnson syndrome is based on the presence of "target" or "iris" lesions involving the skin and erosive lesions of two or more mucosal surfaces. Associated findings include extensive dermal exfoliation, nephritis, lymphadenopathy, hepatitis, and multiple serologic abnormalities. Vancomycin, a glycopeptide antibiotic, has case reports in literature produceing immunologically mediated adverse reactions such as interstitial nephritis, linear IgA bullous dermatosis, exfoliative erythroderma, necrotizing cutaneous vasculitis and toxic epidermal necrolysis. The treatment consists of cessation of vancomycin and administration of antihistamine and/or steroid.

See pic here


References: click to get abstract/article

1.Vancomycin-induced Stevens-Johnson syndrome Allergy Asthma Proc. 1996 Mar-Apr;17(2):75-8.

2.Stevens-Johnson-type reaction with vancomycin treatment. - Ann Pharmacother. 1992 Dec;26(12):1520-1

3 Uncommon Vancomycin-Induced Side Effects - Brazilian Journal of Infectious Diseases - 2002;6(4):196-200

Thursday June 22, 2006
Imipenem and Primaxin

Q: What advantage we have when we add cilastatin with Impenem ?

OR in other words, What is the difference between Imipenem and Primaxin (Imipenem plus Cilastatin) ?


A: Imipenem get metabolized in the kidneys by enzyme called dehydropeptidase I and cannot achive therapeutic level in urine. Addition of Cilastatin inhibit the enzyme in kidney's renal tubules so that when imipenem and cilastatin are given concomitantly, increased imipenem levels are achieved in the urine.

Bonus Pearl: Primaxin is hemodialyzable so dose may be unreliable in such patients or preferably should be given after hemodialysis session. Dose in dialysis dependent patient is either 250 mg q 12 hrs or 500 mg after each dialysis.


When Imipenem was introduced, it get reputed with nick name of "Jesus water" due to its broad coverage and to kill most bugs.

Wednesday June 21, 2006
Normosol is NOT just Normal Saline

Being an intensivist, the most important thing to know - what is infusing in patient. There is some misconception that Normosol is just another name of Normal Saline, which is not true.

Contents of Normal Saline:

Na = 154 mEq/L
Cl = 154 mEq/L
PH = 5.4

Contents of Normosol:

Na = 140 mEq/L
Cl = 98 mEq/L
K = 4 mEq/L
Mg = 3 mEq/L
Acetate = 27 mEq/LGluconate = 23 mEq/L
PH =6.6

Normosol contains added K and Mg which may be unsuitable for some patients like patients with renal failure.

Bonus Pearl: If it says R on IVF bag, it means manufacturer recommends bag for replacement therapy and if it says M on IVF bag , it is meant for maintenance IV. Contents may be little different. Most "M" bags contain extra dextrose.

Related Previous Pearl: Difference between LR and Normal Saline

Labetolol dose

Tuesday June 20, 2006

Labetolol dose

Q: What is the usual guided dose of labetalol in hypertensive emergency ?

A; Loading dose of 0.25 mg/kg followed by 0.5 mg/kg every 15 minutes but total dose should remain less than 3.25 mg/kg.

Advantage of Labetalol:

• Action within 5 minutes and
• combined alpha and beta blocker effect

Disadvantage of Labetalol:

• It decreases both SVR (Systemic Vascular Resistance) and CO (Cardiac Output).

(From Dr. Joseph Varon's lecture "Hypertensive Emergencies in the Perioperative Cardiovascular Setting" at Hypertensive Crisis: Strategies To minimize End-Organ Damage With Focus On The Heart and Brain - symposium during Chest 2005)

Anemia in ICU

Monday June 19, 2006
Anemia in ICU


Q: If you admit a patient with Hb of 10 g/dL and draw 100 ml of blood for various lab works. How much will be the drop in Hb ?


A; Hb will drop from 10 to 9.3 g/dL. With each 100 ml of blood draws, Hb drop by 0.7 g/dL 1. Remember ! phlebotomy (blood draws) is the major of cause anemia in ICUs.

Bonus pearl: In anemic patients, if blood workup is necessary, use pediatric tubes.


Related previous pearl: ICU anemia score


Reference: click to get abstract
Blood testing causes anemia - J Gen Intern Med 2005; 20:520–524

pre-ICU care

Sunday June 18, 2006
To decrease ICU mortality - fix pre-ICU care !!

Team from Cooper University Hospital, Camden, NJ (Raquel Nahra, MD, Christa Schorr, RN and David R. Gerber, DO) - addressed a very important and often ignored issue at ACCP meeting of november 2005 : PRE–INTENSIVE CARE UNIT LENGTH OF STAY AND OUTCOME IN CRITICALLY ILL PATIENTS 1.

Patients were divided into 4 groups:

1. Group M1 - medical patients HLOS less than / = 5 days
2. Group M2 - medical patients HLOS more than / = 6 days
3. Group S1 - surgical patients HLOS less than / =5 but more than 1 day
4. Group S2 - surgical patients HLOS more than / = 6 days

*HLOS = hospital length of stay and data was obtained from the Project Impact database.

Study found that: ICU admission from a general care floor after more than / = 6 days is associated with poor outcome(Group M2). Suboptimal care prior to ICU admission is the reason for poorer outcomes. Probable reasons:

• Poor organization,
• Insufficient knowledge,
• Failure to appreciate clinical urgency,
• Inadequate supervision and
• Failure to seek advice

Editors note: Lessons to be learned include intensivists' early involvement in care outside ICU, formation of rapid response team, close working of floor team (hospitalist) and intensivist and more inservices/training for floor staff.

Related previous pearl: Rapid Response Team
Related Sites: IHI's RRT - getting started kit and SCCM's RRT/ MET forum

Reference: click to get abstract

PRE–INTENSIVE CARE UNIT LENGTH OF STAY AND OUTCOME IN CRITICALLY ILL PATIENTS - Critical Care Outcomes, ACCP meeting November 2, 2005

EKG changes in Hyperkalemia

Saturday June 17, 2006
4 EKG changes in Hyperkalemia


The first EKG sign of hyperkalemia is peaked T waves and usually appears once K level go around 6 meq/L.

Second sign is prolongation of PR interval which can be seen with K level going around or above 7 meq/L.

Absent P wave with widen QRS complex is the third manifestation and is a very dangerous sign. It means that atrial activity is lost and stage is set for ventricular tachycardia/fibrillation. It is usually seen at level around 8-9 meq/L.

Ventricular tachycardia/fibrillation is the price you pay of ignoring above changes on monitor.

Above are just rough rules of thumb. Read a good review

Recognising signs of danger: ECG changes resulting from an abnormal serum potassium concentration (source: Emerg Med J 2002; 19:74-77)

Friday June 16, 2006
Carvediol (Coreg)


Q: How Carvediol (Coreg) is different from other B-blockers?

A; Coreg is a triple blocker. It blocks beta-1, beta-2 and alpha-1 receptors. Alpha-1 blockade provides vasodilation and so protection in congestive heart failure (CHF). U.S. Carvedilol Heart Failure Study with 1094 patients showed 65% lower risk of death than placebo patients 1. Dose should be started at 3.125 mg BID and titrated (as tolerated) upto 25 mg BID. Obese patients may require higher dose.

Extended release Metoprolol (Toprol XL) is another B-blocker approved from FDA for use in CHF. MERIT-HF study showed 34% reduction in mortality than placebo in patients taking Toprol XL 2.

FDA approves only Toprol-XL and Coreg for CHF.



References: Click to get article/abstract

1. The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure - N Engl J Med. 1996;334:1349-1355.

2. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure. Lancet. 1999;353:2001-2007

IV Dig

Thursday June 15, 2006
IV Digoxin


Q: You wrote an order: Digoxin 0.25 mg IV x 1.
What is missing in this order?


A; Rate: Digoxin IV should be given over at least 5 minutes. Rapid infusion of Digoxin (digitalis) may cause coronary arteriolar constriction, which may induce cardiac ischemia or make it worse. Also, it is not advisable to administer digoxin simultaneously in the same intravenous line as with other drip/drug, if possible. Another important reminder - Digoxin level should be measured just before the next scheduled dose (trough) or at least 6 to 8 hours after the last dose, to allow adequate time for equilibration of digoxin between serum and tissue.


Related previous pearl: Why sometime IV vasotec (enalapril) does not work?

Wednesday June 14, 2006
Swan is still very in !!


Lately we had some constant negative studies for pulmonary artery catheter like ESCAPE trial, PAC-MAN study and recently published ARDSnet's FACTT trial 2.

This month Critical Care Medicine published retrospective database analysis of 53,312 trauma patients 1. After all adjustments following groups showed benefit:

• Patients aged 61-90 yrs,
• with arrival base deficit worse than -11 and
• Injury Severity Score of 25-75.

It was found that it was associated with a protective effect in patients with severe shock, regardless of age, and in older patients with moderate shock.

Also note negative outcome: Highest risk of death associated with PAC use was in younger patients who arrived at the ED without a significant base deficit. Moreover, no survival benefit was detected with PAC use in patients arriving at the ED without evidence of shock.

Conclusion: PAC insertion is associated with

1. improved outcome in critically injured patients with severe shock at admission, regardless of age, and
2. in elderly patients with moderate shock.

Related previous pearls: PAC-MAN study ! and ESCAPE Trial



Reference: Click to get article

1. Pulmonary artery catheter use is associated with reduced mortality in severely injured patients: A National Trauma Data Bank analysis of 53,312 patients - Critical Care Medicine. 34(6):1597-1601, June 2006.
2. Pulmonary-Artery versus Central Venous Catheter to Guide Treatment of Acute Lung Injury - Volume 354:2213-2224, NEJM, May 25, 2006

CVP via PICC

Tuesday June 13, 2006

Can we measure CVP (central venous pressure) with PICCs (peripherally inserted central catheters) ?


YES: PICC lines can be used to measure CVP, if situation arise. CVP recorded via PICC lines are about 1 mm Hg higher than CVP from centrally inserted venous catheters. PICC lines need to be hooked to continuous infusion with heparinized saline at 3 mL/hr to overcome the resistance of longer length and narrower lumen of PICC line. Trend should be followed for better perception as first PICC measured CVP is reported higher, probably due to microthrombi which get flushed later on.

Dr. Black and coll. from Pennsylvania State University College of Medicine, Hershey, PA studied 77 data pairs from 12 patients with measurements recorded at end-expiration. 19-gauge dual-lumen PICCs were used and were zeroed/levelled at right atrium. To overcome the longer length, narrower lumen an so higher inherent resistance, continuous infusion device is used with heparinized saline at 3 mL/hr (like in arterial lines) 1.


Reference: Click to get article

1. Central venous pressure measurements: Peripherally inserted catheters versus centrally inserted catheters - Critical Care Medicine. 28(12):3833-3836, December 2000.

Monday June 12, 2006

While you are carrying 'code beeper' as an intensivist, you heard 'code blue in cafeteria'. On arrival you found 36 year old female who was in cafeteria after visiting allergy clinic, where according to daughter she received her 'expensive asthma shot'. While you were resuscitating patient from what appears to be anaphylactic shock, you keep wandering about that 'expensive asthma shot'.


Xolair: Omalizumab (xolair) is the subcutaneous injection treatment for allergic asthma that works by blocking immunoglobulin E (IgE). Anaphylaxis is rare but the tricky part is it may cause anaphylaxis even after months of successful and uneventful treatment. There is an indication in atleast one case report that polysorbate present in omalizumab may be responsible for it 1.

Per month cost of treatment is about 500 - 2000 US $.


Reference: Click to get article

1. Late-Onset Anaphylaxis to Omalizumab Reported - from acep.org site

IV to PO conversion

Sunday June 11, 2006
IV to PO conversion - check med list everyday !!


58 year old male admitted with atrial fibrillation with RVR (rapid ventricular rate) and required intravenous (IV) Diltiazem (cardizem). Now patient is stable at 7 mg/hr dose. What would be the equivalent PO dose?


Diltiazem CD 240 mg po qd 1.

Usual IV to PO Cardizem is as follows:

3 mg/h = Diltiazem CD 120 mg po qd
5 mg/h = Diltiazem CD 180 mg po qd
7 mg/h = Diltiazem CD 240 mg po qd
11 mg/h = Diltiazem CD 300 mg po qd
15 mg/h = Diltiazem CD 360 mg po qd


Using this question as an excuse, the objective is to highlight the point that many times PO medications are as effective as IV (See reference # 1). Good intensivist always remain in the quest to simplify the medication list. It always help to have a savy critical care pharmacist in the team !.


Related: Sample INTRAVENOUS TO ORAL/ENTERAL (IV TO PO) MEDICATION SWITCH PROGRAM from American Society of Health-System Pharmacists' site


Reference: click to get abstract/article
1. Intravenous to Oral Conversion Table: source nih.gov

Feeding in ventilated patients

Saturday June 10, 2006
Yes ! Feed Critically Ill Mechanically Ventilated Medical Patients early despite risk of VAP


There is some hesitancy in literature about early feeding for critically ill mechanically ventilated medical patients due to increase risk of ventilator-associated pneumonia (VAP) 1.

Dr. Artinian and coll. from Division of Pulmonary and Critical Care Medicine, Henry Ford Health System, Detroit, MI recently looked into about 4000 patients requiring mechanical ventilation for more than 2 days 2. Those patients who received enteral feeding within 48 hours of mechanical ventilation were labeled as the "early feeding group" otherwise as "late feeding group." Results showed that

• The overall ICU mortality was 18.1% vs 21.4%
• The overall hospital mortality was 28.7% vs 33.5%

In substudy, three separate models were done using APACHE II, simplified acute physiology score II, and mortality prediction model at time 0. In all models, early enteral feeding was associated with

• an approximately 20% decrease in ICU mortality
• a 25% decrease in hospital mortality
• The lower mortality rates in the early feeding group were most evident in the sickest group

The truth was found that in all adjusted analysis, early feeding was found to be independently associated with an increased risk of ventilator-associated pneumonia (VAP).

Study concluded that early feeding significantly reduces ICU and hospital mortality mainly in the sickest patients and should be instituted in medical patients receiving mechanical ventilation especially in patients at high risk of death, despite being associated with an increased risk of VAP developing.

Related previous pearls:
Where is my food dude !! and Is post pyloric feeding absolute ?

Reference: click to get abstract/article
1. Early versus late enteral feeding of mechanically ventilated patients: results of a clinical trial - Journal of Parenteral and Enteral Nutrition, Vol 26, Issue 3, 174-181
2. Effects of Early Enteral Feeding on the Outcome of Critically Ill Mechanically Ventilated Medical Patients - Chest. 2006;129:960-967

Friday June 9, 2006


Case: 76 year old female, admitted 3 days ago to your ICU with possible aspiration pneumonia. Review of report from nursing home also mention of increase diarrhea. You decide to add metronidazole (flagyl) and start the workup. Patient responded well to treatments and appears to be back to her baseline. You decide to keep patient overnight before transferring to floor in AM. Patient complaint of epigastric abdominal pain during night and on-call physician added pancreatic enzymes for AM and lipase is noted to be 1254 (was normal on admission). You could not find any apparent reason of acute pancreatitis. As C.diff came back negative you stopped the Flagyl and pancreatitis resolved.


Metronidazole Induced Pancreatitis: Acute pancreatitis is a potentially serious adverse effect of metronidazole. Any patient while on metronidazole develops nausea, vomitting and epigastric pain should be evaluated for acute pancreatitis. Acute pancreatitis may develop upto 5 weeks after metronidzole exposure and drug intake in previous weeks should be evaluated carefully particularly in long term care facility residents. Diagnosis can be confirmed with rechallenge with metronidazole but obviously it should be avoided. The mechanism of metronidazole-induced pancreatitis is not known but unlike many other antibiotics metronidazole penetrates well into pancreatic tissue and explains atleast part of the problem.


Reference: click to get abstract/article
1. Metronidazole Induced Pancreatitis. A Case Report and Review of Literature - JOP. J Pancreas(Online) 2004; 5(6):516-519
2. Metronidazole-associated pancreatitis - The Annals of Pharmacotherapy: Vol. 34, No. 10, pp. 1152-1155
3. Acute pancreatitis caused by metronidazole - Ned Tijdschr Geneeskd. 1996 Jan 6;140(1):37-8.

Thursday June 8, 2006
What if plasma exchange is not available as treatment of TTP


Q: You just diagnosed a patient with thrombotic thrombocytopenic purpura (TTP) but you were informed by the nursing supervisor that plasma exchange with fresh frozen plasma is not available in hospital due to technical reason and it will take time before patient can be transferred to a facility where the said services are available. What would be your alternate plan to bridge that time?


A; High-dose plasma infusion with rate of 25-30 mL/kg per day. When immediate plasma exchange with fresh frozen plasma is not available, simple plasma infusion can be performed until transfer to a higher care facility is available. There is always a substanial risk of fluid overload with such high plasma infusion and you have to weigh risks and benefits of the clinical decision or to watch patient closely while plasma is infusing.


Reference: click to get abstract/article

High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome - Medicine. 82(1):27-38, January 2003.

acetazolamide for metabolic alkalosis

Wednesday June 7, 2006
Dose of acetazolamide (diamox) for metabolic alkalosis


Many times we use acetazolamide for metabolic alkalosis in mechanically ventilated patients when nothing else is making it better. What dose should we use?. Mazur and coll. from Henry Ford Health System, Detroit, MI looked into 40 mechanically ventilated patients with a metabolic alkalosis (arterial pH more/= 7.48 and serum bicarbonate concentration more/= 26 mEq/L) which were resistant to other therapies such as fluid infusion or potassium therapy.

Study found that a single IV 500-mg dose of acetazolamide is as effective as multiple doses of IV 250 mg of acetazolamide.


Reference: click to get abstract/article

Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: A randomized, double-blind trial. Critical Care Medicine. 27(7):1257-1261, July 1999.

Wells Score of DVT

Tuesday June 6, 2006
Wells Score of DVT

Pulmonary embolism from deep venous thrombosis remains a leading killer. Many times intensivists are faced with the question of proceeding or not with further radiological workup. Although Wells score is not the absolute score to rule out DVT and subsequently the risk of PE (some literature argue against its validity), it still remains a strong quick tool while differential diagnosis with other conditions. It has been said that if the score of low-probability is combined with negative d-dimer, the negative predictive value is 99.5% 1. In other words, you can safely hold on further radiological workup.

3 points if objective signs like localized tenderness, asymmetric calf swelling.
1.5 points if Heart Rate more than 100 beats/min
1.5 points if bedridden for more than 3 days or major surgery within 4 weeks
1.5 points if previous 'documented' diagnosis of DVT or PE
1 point if hemoptysis
1 point if active cancer
3 points if high clinical suspicion of PE (on overall clinical and lab. findings).

• 0 - 2 low probability,
• 2-6 moderate probability,
• 3-6 high probability

Remember,

low-probability + negative d-dimer = -ve predictive value of not having DVT is 99.5%

Related previous pearl: What if even thrombolysis fails in massive PE ?


Reference: click to get abstract/article
Excluding Pulmonary Embolism at the Bedside without Diagnostic Imaging: Management of Patients with Suspected Pulmonary Embolism Presenting to the Emergency Department by Using a Simple Clinical Model and D-dimer Philip S. Wells and coll.,Ann Intern Med 2001;135:98-107

Four generations of Quinolones

Monday June 5, 2006
Four generations of Quinolones


The classification of the fluoroquinolones on the basis of generations (imitating from cephalosporins) is not officially standardized, but it is now commonly use to classify them by their spectrum of action.


1st generation - Gram negative coverage but not pseudomonas (example: Nalidixic acid)

2nd generation - Gram negative coverage with pseudomonas and some gram postive coverage including s.aureus but not strep pneumoniae. (example: Ciprofloxacin, Ofloxacin, Norfloxacin)

3rd generation - Gram negative coverage with pseudomonas. More gram postive coverage including penicillin sensitive and resistant s. pneumoniae. (example: Levofloxacin, Sparfloxacin, Gatifloxacin (tequin), Moxifloxacin (avalox)). Avalox has been said to be the most effective in this generation.

4th generation - Same as 3rd generation but with anaerobic coverage (example: Trovafloxacin (Trovan) ).



Read comprehensive review on Quinolones (Source: Am Fam Physician 2002;65:455-64, authors: CATHERINE M. OLIPHANT, PHARM.D., University of Wyoming School of Pharmacy and GARY M. GREEN, M.D., Kaiser Permanente, California)

Quinolones in UTI

Sunday June 4, 2006
Quinolones in UTI


Q; Name atleast one quinolone which should not be used for UTI in ICU ?

A: Moxifloxacin (avelox) - as it doesn't reach sufficient level in the urine. On the flip side, the advantage is that you don't need to adjust dose in renal insufficiency unlike other quinolones if use for other reasons. Similarly, Sparfloxacin (Zagam) and trovafloxacin (Trovan - almost off the market due to severe hepatic side effects) should not be used as these 3rd and 4th generation quinolones are more metabolized through liver.

Urinary tract infection (UTI) is a common and many time an isolated or accidental finding in ICU. Rememeber ! Bactrim (TMP/SMX) is still a first line, cost-effective and preferred antibiotic for uncomplicated UTIs. You should jump to quinolone only if your hospital's antibiogram shows local resistance higher than 20% or if patient is allergic to sulfas. Even in this instance nitrofurantoin is a very valid choice. If you decide to use quinolone - ciprofloxacin, ofloxacin, or norfloxacin is a better choice. Levofloxacin is also commonly prescribed but technically it is not really needed for UTI and just contribute to increase resistance in ICU by overuse.


Previous related pearls:

1. Quinolones and errant glycemic reaction

2. Epidemic of new fluoroquinolone induce strain of C. Diff.

Saturday June 3, 2006


Q; Which one electrolyte you will be worried most in patients on TPN (Total Parenteral Nutrition) ?

A; Phosphate. About 33% of patients on TPN develop hypophosphatemia despite supplemented in solution. Patients who require insulin during TPN, or have a history of alcoholism, chronic weight loss, cancer and on diuretic therapy are at increased risk of hypophosphatemia, which also may manifest as "Refeeding syndrome". Serum phophate level below 1.5 mg/dl ( .5 mmol/L), can manifest symptoms of refeeding syndrome.

Read interesting editorial, Refeeding syndrome, Is underdiagnosed and undertreated, but treatable , from BMJ. ( BMJ 2004;328:908-909 )



References: click to get abstract/article

1. Refeeding syndrome: life-threatening, underdiagnosed, but treatable, QJM, April 1, 2005; 98(4): 318 - 319.

4 Ts of HIT

Friday June 2, 2006
4 Ts of HIT

Continuing our theme of Heparin-Induced Thrombocytopenia (HIT) from yesterday, lets talk today about "4 Ts" of HIT.

Thrombocytopenia - more than 50% fall

Timing of platelet count fall - Days 5 to 10, or less than/= 1 day if heparin exposure within past 30 days

Thrombosis or other sequelae - Proven thrombosis, skin necrosis, or, after heparin bolus, acute systemic reaction

Other cause for thrombocytopenia - None

American Society of Hematology has developed a full HIT score which can be seen by clicking here. 1

References: click to get abstract/article

1. When Heparins Promote Thrombosis - Review of Heparin-Induced Thrombocytopenia - Circulation. 2005;111:2671-2683

Thursday June 1, 2006
Argatroban Therapy in Hepatic Dysfunction


Argatroban is a second line anti-coagulation as well as remained one of the drug of choice in patients affected with Heparin-induced thrombocytopenia (HIT). Argatroban improve outcomes in patients with HIT, by reducing new thrombosis 1 . Also reported its safety with no increase risk of bleeding 2 .

Argatroban is primarily metabolized in the liver and its dosing need to be adjusted in hepatic dysfunction. Dr. Levine and coll. from Texas has reported in this month of chest after retrospectively analysing data of 82 argatroban patients and 34 historical control therapy patients with hepatic impairments (all HIT patients) 5. Their results concluded following points:

1. In hepatic impairment 0.5 µg/kg/min is a reasonable, conservative initial dosage of argatroban.

2. serum bilirubin level appears to be a better indicator than ALT or AST of argatroban dosing requirements and argatroban should be initiated at a dose of 0.5 µg/kg/min if a patient’s serum total bilirubin level is 1.5 mg/dL.

3. Conservatic dose should be the starting point if combined hepatic/renal dysfunction is present.

4. As steady-state anticoagulation will be delayed in many patients with hepatic dysfunction, check the aPTT atleast 4 to 5 h after drug initiation or dose change.

5. Argatroban should be stopped for a more extended period in hepatic dysfuntion if an invasive procedure is planned.


Related: Sample Argatroban Protocol For HIT (from The George Washington University Hospital )


References: click to get abstract/article

1. Argatroban Anticoagulation in Patients With Heparin-Induced Thrombocytopenia - Arch Intern Med. 2003;163:1849-1856
2. Argatroban Anticoagulant Therapy in Patients With Heparin-Induced Thrombocytopenia - Circulation. 2001;103:1838
3. The Pharmacokinetics and Pharmacodynamics of Argatroban: Effects of Age, Gender, and Hepatic or Renal Dysfunction - Pharmacotherapy 2000;20,318-329
4. Argatroban Dosing in Patients with Heparin-Induced Thrombocytopenia The Annals of Pharmacotherapy: Vol. 37, No. 7, pp. 970-975.
5. Argatroban Therapy in Heparin-Induced Thrombocytopenia With Hepatic Dysfunction Chest. 2006;129:1167-1175