Post fellowship shock syndrome

Sunday April 30, 2006
Post fellowship shock syndrome

Q; What is Post fellowship shock syndrome ?

A; Post fellowship shock syndrome is a kind of culture shock for young graduates when they transit from big tertiary care academic centers to regular community based medical practice. Transit from high tech, literature oriented, academic based and superior nursing quality to business oriented, "thats how we do things here" practice, no house staff support, no billing experience and wide spectrum of nursing quality - caught unprepared young graduates with mental and culture shock and may leave them frustrated with present situation. Its important to prepare graduating residents and fellows for future practice of medicine.

Read related article The Realities of the First Year of Practice ( NEJM CareerCenter )

(Post fellowship shock syndrome is a term invented by editors of this web-site)

Iodide in Thyroid Storm

Friday April 28, 2006
Iodide in Thyroid Storm

Q; How long should you wait to administer iodide after giving antithyroid medication in the management of thyroid storm ?

A; Atleast one hour.


Oral or rectal iodide compounds block release of thyroid hormones after starting antithyroid drug therapy. But if given early in management (before antithyroid medication become effective) it can get utilize in the synthesis of new thyroid hormone. Read nicely written review on Thyroid Storm (and Myxedema coma) by Nikolaos Stathatos, MD, and Leonard Wartofsky, MD from Washington Hospital Center in Washington, D.C. - ref.: emedmag.com, 02/15/2003 issue.

IV steroid in postextubation stridor

Thursday April 27, 2006
IV steroid to reduces postextubation stridor

Interesting study came out in May' 2006 issue of Critical Care Medicine regarding intravenous injection of methylprednisolone to reduce the incidence of postextubation stridor in intensive care unit patients. 128 patients who were intubated for more than 24 hrs with a cuff leak volume less than 24% of tidal volume but met weaning criteria were studied. 128 patients were divided into 3 groups.

• placebo group (n = 43) with four injections of normal saline every 6 hrs,
  
• 4 INJ group (n = 42) with four injections of methylprednisolone (40 mg every 6 hours)
  
• 1 INJ group (n = 42) with one injection of the methylprednisolone (40 mg) followed by three injections of normal saline.

Extubation done one hour after last injection. Postextubation stridor was confirmed by examination using bronchoscopy or laryngoscopy.

Results shows that:
The incidences of postextubation stridor were lower both in the 1 injection (11.1%) and the 4 injections groups (7.1%) than in the control group (30.2%,). The side effects of steroids over 24 hrs were minimal with no obvious complications such as GI bleed, hyperglycemia, or increased risk of infection.

Please read full study for inclusion exclusion criteria, all outcomes, comparision with non-intervention group of 193 patients and discussion of study by authors.

Related previous pearl: Cuff leak tests

References: click to get abstract
1. Intravenous injection of methylprednisolone reduces the incidence of postextubation stridor in intensive care unit patients - Critical Care Medicine. 34(5):1345-1350, May 2006

LaSRS

Wednesday April 26, 2006

LATE STERIOD RESCUE STUDY (LaSRS): The Efficacy of Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome.

Finally the results of ARDSnet's LaSRS trial are published. Out of 180 patients with ARDS of atleast 7 days, 91 were randomly assigned to the placebo group and 89 to the methylprednisolone group. Some outcomes are very unexpected :

1. There was no significant difference in the 60-day hospital mortality rate, with 26 deaths in each group.

2. At 180 days, 29 patients had died in the placebo group and 28 had died in the methylprednisolone group.

3. The methylprednisolone group had significantly more ventilator-free days than the placebo group during the first 28 days as well as at 180 days.

4. As compared with the placebo group, the methylprednisolone group also had significantly fewer days in the ICU during the first 28 days but not at day 180 !!.

5. Ventilatory assistance was resumed: 6 in the placebo group and 20 in the methylprednisolone group. Also 8 of the 20 methylprednisolone-treated patients who resumed receiving assisted ventilation died, as compared with 3 of 6 patients in the placebo group.

6. The mean serum glucose level was not significantly different between groups at baseline but was significantly higher in the methylprednisolone group than the placebo group on days 1, 2, and 4.

7. Forty-three serious infections were diagnosed in 30 patients in the placebo group, as compared with 25 serious infections in 20 patients in the methylprednisolone group.

8. There were 17 episodes of septic shock among 15 patients in the placebo group and 6 episodes among 5 patients in the methylprednisolone group.

9. Prospectively, serious neuromyopathy were reported in nine patients, all of whom were in the methylprednisolone group but interestingly retrospective chart review found no significant difference in the incidence of neuromyopathy: 21 in the placebo group and 27 in the methylprednisolone group. Also, Exposure to neuromuscular-blocking agents was not significantly more common among patients who were identified as having neuromyopathy.

10. Patients who were enrolled at least 14 days after the onset of ARDS and who were randomly assigned to receive methylprednisolone had a significantly higher case fatality rate than similar patients who were assigned to receive placebo.

Study conclusion: These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting steroid therapy more than two weeks after the onset of ARDS may increase the risk of death.

Editor note: Please read whole article to be aware of limitations of study.

References:
1. Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome - Volume 354:1671-1684, Number 16, April 20,2006
2. Protocol of study: ARDSnet.org
3. Late Steroid Rescue Study (LaSRS): The Efficacy of Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome - clinicaltrials.gov

Esophageal Pressure Measurements and compliance

Tuesday April 25, 2006
Esophageal Pressure Measurements and compliance

At bedside compliance is measured as

Cs = Vt / Ppl - (PEEP + autoPEEP)

Where Cs = compliance of static thorax, Vt = tidal volume, Ppl = plateau pressure and PEEP is postive-end-expiratory pressure

or in more precise terms

C stat = Vt / (Pao end'inhalation - Pao end'exhalation)

Where Pao = pressure at the airway opening. Pao end'inhalation is same as Ppl. and Pao end'exhalation is same as TotalPEEP.

This compliance measures the whole thorax including chest wall and lungs. Normal Cs is ideally 100 ml/cm H2O or practically 50 to 80 ml/cm H2O is acceptable.

Placement of esophageal catheter can give lung compliance (CL) and chest wall compliance (Ccw) separately. Formulae are

CL = Vt / (Pao - Pes) end'inhalation - (Pao - Pes) end'exhalation
and
Ccw = Vt / (Pes - Patm) end'inhalation - (Pes - Patm) end'exhalation
or practically done simply as Ccw = Vt / Pes end'inhalation

Where Pes = Esophageal pressure and P atm = Atmospheric pressure

Normal CL and Ccw is 200 ml/cm H2O.


Read article Esophageal and Gastric Pressure Measurements , including all the basics of how to insert and measure the esophageal catheter pressures by Dr. Joshua O Benditt (ref: Resp. Care, Jan. 2005, vol 50, no. 1)

CURB-65 Score

Monday April 24, 2006
CURB-65 Score

Lim and colleagues have designed a score called CURB-65 to rate mortality in community acquired pneumonia (CAP) - based on information available at initial hospital assessment. Give one point each for following values

C = Confusion
U = Urea (BUN) if more than 20 mg/dl (7 mmol/l)
R = Respiratory rate if more than / = 30/min,
B = BP if syst. less than 90 mm Hg or diast. less than/= 60 mm Hg,
65 = If age more than / = 65 years

With score 0 expected mortality is 0.7%,
With score 1 expected mortality is 3.2%,
With score 2 expected mortality is 13%,
With score 3 expected mortality is 17%,
With score 4 expected mortality is 41.5% and
With score 5 expected mortality is 57%

References:
1.Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study - W S Lim, M M van der Eerden, R Laing, W G Boersma, N Karalus, G I Town, S A Lewis and J T Macfarlane - Thorax 2003;58:377-382

Hemodynamic variables in septic shock

Sunday April 23, 2006
Hemodynamic variables to watch in septic shock

Dr Varpula and coll. from Helsinki, Finland tried to identify the most related hemodynamic variables in 111 septic shock patients. Data from 6 hours and 48 hours were analyzed separately. Primary endpoint was 30-day mortality. Following results were found:

1. Univariate analysis showed that lactate level on arrival and MAP-derived variables (average of all MAP values, hypotension time) during the first 6 hours correlated with the 30-day mortality.

2. The best cutoff values for hypotension and hypoperfusion times were found to be MAP of 65 mmHg and SvO2 of 70%, respectively.

In conclusion, data suggest that time spent with low BP and with inadequate CO (decrease SvO2) are the most important hemodynamic variables related to outcome. This study find threshold values in synchrony with values published in recent guidelines.

Related Sites: survivingsepsis.org

Related Previous pearls: Shock alert , ScvO2 or SvO2 ? and EGDT and PAC need


References:
1.Hemodynamic variables related to outcome in septic shock - Intensive Care Medicine, Volume 31, Number 8 , August 2005, Pages: 1066 - 1071

Law of LaPlace

Saturday April 22, 2006
Law of LaPlace, PEEP and surfactant

Law of LaPlace tells us that "Pressure is always greater in smaller radius".

P = 2T/r

where P = pressure, T = tension and r = radius

So in lungs, smaller alveoli will have greater resistance for air to flow during inspiration because of higher pressure. We use PEEP to keep alveoli open during expiration (prevent derecruitment), as name says positive end-expiratory pressure. High tidal volume cause more shear force damage to smaller alveoli with each breath to overcome this pressure. Thats why, our present approach to ventilator management in ARDS is low tidal volume and optimum PEEP (See ARDSnet

Lower Tidal Volume/ Higher PEEP Reference Card).

Looking at same formula, other approach is to decrease Tension, by nature's method of applying surfactant. One study published in August 2004 looked into 'Effect of Recombinant Surfactant Protein C–Based Surfactant on the Acute Respiratory Distress Syndrome' and found no significant difference in terms of 28 days mortality or the need for mechanical ventilation but also showed that 'Patients receiving surfactant had a significant greater improvement in blood oxygenation during the first 24 hours of treatment than patients receiving standard therapy'. Actually literature suggests that "..Sufficient levels of PEEP will also help to prevent further loss of surfactant in still ‘healthy’ alveoli,"

Read Professor Lachmann's lecture -

Current status of lung protective ventilation in ARDS, discussing Law of LaPlace, surfactant and PEEP. (source: eacta.org - European Association of Cardiothoracic Anaesthesiologists)

References:
1.Effect of Recombinant Surfactant Protein C–Based Surfactant on the Acute Respiratory Distress Syndrome - Volume 351:884-892, Number 9, NEJM Aug. 26, 2004
2. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome - The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network ,Volume 351:327-336, Number 4, NEJM, july 22, 2004

ketek

Friday April 21, 2006

Case: 74 year old male resident of assisted living facility, admitted to ICU with exacerbation of his myasthenia gravis. He also reports newly devloped symptoms of blurred vision, difficulty focusing, and diplopia which according to him is not typical of his symptoms but you assume it as part of exacerbation of myasthenia gravis. Patient denies stopping his medicine. 3 days ago he was seen by his primary care physician for cough and was given samples of a new strong antibiotic. His neurologist has been consulted who requests you to change his antibiotic. Patient symptoms resolved within 24 hours.

Answer: Ketek (Talithromycin) is a first ketolide (cousin of macrolide), indicated for mild to moderate acute exacerbation of chronic bronchitis, acute bacterial sinusitis and in mild to moderate CAP, atypical and multi-drug resistant strains of S pneumoniae. Talithromycin unlike the macrolides has 2 strong binding sites on the bacterial ribosome and this strong dual binding helps provide coverage against resistant strains of S pneumoniae. Exacerbations of myasthenia gravis have been reported in patients with myasthenia gravis treated with Talithromycin. It cause visual disturbances like blurred vision, difficulty focusing, and diplopia by slowing the ability to accommodate and the ability to release accommodation. Other major side effects include hepatic dysfunction and potential to prolong the QTc interval.


References:
1. FDA Public Health Advisory Ketek (telithromycin) Tablets - fda.gov
2. FDA consumer info. - fda.gov
3. www.ketek.com

Ambien

Thursday April 20, 2006
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:
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

US guided radial artery

Wednesday April 19, 2006
Ultrasound guided insertion of radial artery catheters

Role of ultrasound guidance in central venous catheter (particularly internal jugular vessel) is well known 1 but literature on its efficacy in arterial line insertion is very scant. Levin and coll. from Hadassah University Hospital, Jerusalem, Israel has done a simple but interesting study on the use of ultrasound guidance in the insertion of radial artery catheters 2. A total of 69 patients were randomized - 34 to the ultrasound group and 35 to the palpation group. The following results were found:

* The arterial cannula was inserted on the first attempt in 21 of the 34 patients (62%) in the ultrasound group vs. 12 of the 35 patients (34%) in the palpation group.

* Overall, there were 55 total attempts (1.6 per patient) at arterial catheter insertion in the ultrasound group vs. 110 (3.1 per patient) in the palpation group.

* The mean overall time taken per patient for catheter insertion was 55.5 secs in the ultrasound group vs. 111.5 secs in the palpation group.

* In the ultrasound group, a total of 39 cannulae were used vs. 60 in the palpation group (cost effectiveness).


References:
1 Bedside Ultrasonography in the ICU Part 2 - Chest. 2005;128:1766-1781
2. Use of ultrasound guidance in the insertion of radial artery catheters - Critical Care Medicine: Volume 31(2) February 2003 pp 481-484

Wernicke's Encephalopathy

Tuesday April 18, 2006
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 full review article Wernicke's encephalopathy from Philip Salen, MD at emedicine.com

Tacrolimus

Sunday April 16, 2006

Case: 34 year old male with recent kidney transplant admitted to your unit with mental status change and family reports witnessed seizure. While evaluating patient, nurse hand over critical lab to you with magnesium of 0.2 mg/dl, your first response is to ask potassium level but it is actually on hyperkalemic side with 5.5 meq/l. As you call his renal transplant physician and reports severe hypomagnesemia and seizure but normal BUN/Cr level, his first question is to read patient's medication list. Why ?

Tacrolimus (FK-506 or Prograf) is a macrolide, an immunosuppressive drug, use in organ transplant to reduce the risk of organ rejection. It causes hyperkalemia due to renal tubular acidosis, Type 4 (RTA-IV) but simultaneously cause hypomagnesemia, unusual to find both together. Other side effects of tacrolimus includes seizures, tremors, hypertension, confusion, calciuria, hyperglycemia, weakness, depression, cramps, and neuropathy. Apart fron side effect of severe hypomagnesemia, seizure and other neural are direct effects of tacrolimus too.

References:
1. Downregulation of Ca2+ and Mg2+ Transport Proteins in the Kidney Explains Tacrolimus (FK506)-Induced Hypercalciuria and Hypomagnesemia - J Am Soc Nephrol 15:549-557, 2004
2. FK 506-induced neurotoxicity in liver transplantation. - Wijdicks EF, Wiesner RH, Dahlke LJ, Krom RA. - Ann Neurol 1994;35:498–501.
3. Prograf Warning Letter - fda.gov
4. Tacrolimus leukoencephalopathy: A neuropathologic confirmation Lavigne et al. Neurology.2004; 63: 1132-1133
5. Progressive neurological disease induced by tacrolimus in a renal transplant recipient: Case presentation - BMC Nephrology 2006, 7:7

Nasal cannula after extubation

Saturday April 15, 2006
Nasal cannula vs Face mask after extubation

Technically, there is no advantage of applying face mask after extubation. Nasal cannula is actually better as it is not only cost effective, it provides greater comfort for patients. Face mask is required only when patient is extubated from high FiO2 or if there is a suspicion of oxygen flow interruption via nasal route.

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


References:
1. Critical Care Medicine: The Essentials - Third Edition by John J. Marini. Arthur P. Wheeler - Page 318
2. Use of nasal cannula versus face mask after extubation in patients after cardiothoracic surgery - Critical Care Nurse, Vol 21, Issue 3, 47-53

Allen test

Friday April 14, 2006
A-line is here but where is Allen test !!

Its true that the usefulness of Allen test has never been tested in a big trial but it remained the recommended part before obtaining (radial) arterial blood gas or inserting (radial) arterial line as the whole concept makes common sense. But unfortunately, many times this is the most ignored part of whole procedure. Allen test was developed by legendary cardiologist from mayo clinic, Edgar Van Nuys Allen (1900 - 1961). He is well-known for his work on the administration of anti-coagulant, dicumerol to humans.

With the hand elevated and patient making fist (about 15 seconds), firm pressure applied against radial and ulnar arteries, which leads to blanching of the hand. Then, one of the arteries is released and, in the normal case the blanching disappears over the whole of the hand within 5 to 7 seconds. Test should be repeated with both arteries.

The New England Journal of Medicine has posted the free video on Placement of an Arterial Line (also demonstrating Allen test). Click here to see the link. (Volume 354:e13 - April 13, 2006)


reference:
1. Edgar Van Nuys Allen - whonamedit.com

Fan Score

Thursday April 13, 2006
Fan Score (Hong-Kong criteria or 20/200 Score)

Why we don't hear about the most easiest way to assess the severity of acute pancreatitis, with only 2 parameters:

1. Azotemia - BUN more than 20 mg/dL (7.4 mmol/L)
and/or
2. Glycemia - more than 200 mg/dL ( 11 mmol/L)

Reason this criteria failed to gain ground, is conflicting reports in literature. Originally, Fan and colleague reported the sensitivity of 76% and specificity of 75% but later 2 studies failed to confirm the high sensitivity (only 33% 4 and 52% 3 respectively). Study in reference # 3 also found that best prediction to severity of acute pancreatitis was provided by the APACHE II score 24 hours post admission with sensitivity of 79% and specificity of 82% . Famous Ranson criteria in same study showed sensitivity of 79% but specificity was only 56%


Related article: New Serum Markers for the Detection of Severe Acute Pancreatitis in Humans - Am. J. Respir. Crit. Care Med., Volume 164, Number 1, July 2001, 162-170



References: (click to get abstrat/article)

1. Assessment of severity of acute pancreatitis: a comparison between old and most recent modalities used to evaluate this perennial problem - World J Gastroenterol 1999; August 5(4):283-285
2. Fan ST, Choi TK, Lai ECS, Wong J. Prediction of severity of acute pancreatitis: an alternative approach. - Gut,1989;30:1591-1595
3. Failure of the Hong Kong criteria to predict the severity of acute pancreatitis - Int J Pancreatol. 1997 Dec;22(3):201-6.
4. The Hong Kong criteria and severity prediction in acute pancreatitis - Int J Pancreatol. 1994 Jun;15(3):179-85.

Simplified Glasgow score

Wednesday April 12, 2006
Simplified Glasgow score for the assessment of severe acute pancreatitis

There have been many scores/criterias proposed for the assessment of severe acute pancreatitis including but not limited to Ranson criteria, Glasgow score, Fan score (Hong-Kong criteria), CT-scan score. Although ranson criteria remained popular, glasgow score has been said to be more precise, which is as follows:


Finding at any time during initial 48 hours - give 1 point for each parameter.

age more than 55 years
serum albumin more than 3.2 g/dL
arterial pO2 on room air more than 60 mm Hg
serum calcium more than 8 mg/dL
blood glucose more than 180 mg/dL
serum LDH more than 600 U/L
serum urea nitrogen more than 45 mg/dL
WBC count more than 15,000/mm3


Total score more than / = 3 severe pancreatitis likely.
Total score less than / = 3 severe pancreatitis is unlikely.


Related Previous Pearl:
Evidence-based recommendations for Severe Acute Pancreatitis)


References: (click to get abstrat/article)

1. Assessment of severity of acute pancreatitis: a comparison between old and most recent modalities used to evaluate this perennial problem - World J Gastroenterol 1999; August 5(4):283-285
2. Predictive evaluation of acute necrotizing pancreatitis: results of a prospective study - Presse Med. 1995 Feb 4;24(5):263-6.
3. A simplified method for computed tomographic estimation of prognosis in acute pancreatitis - Scand J Gastroenterol. 2003 Apr;38(4):433-6.
4. Management of the critically ill patient with severe acute pancreatitis - Critical Care Medicine: Volume 32(12) December 2004 pp 2524-2536 . Sponsored by the American Thoracic (ATS), the European Respiratory Society (ERS), the European Society of Intensive Care Medicine (ESICM), the Society of Critical Care Medicine (SCCM) and the Société de Réanimation de Langue Française (SRLF).

Fondaparinux in Acute Coronary Syndromes

Tuesday April 11, 2006
Is Fondaparinux (arixtra) superior in Acute Coronary Syndromes ?

2 major studies published this week in The New England Journal of Medicine and JAMA regarding anticaogulation with Fondaparinux (arixtra) in Acute Coronary Syndromes.

NEJM: 20,078 patients with acute coronary syndromes were randomized either to receive fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days. The primary outcome were death, myocardial infarction, or refractory ischemia at nine days.The number of patients with primary-outcome events was similar in the two groups (579 with fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; But the rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent].Study concluded that Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity 1,2,3.

JAMA: Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12092 patients with STEMI from 41 countries. Patients were divided into 2 strata. 1. fondaparinux initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin is not indicated). 2. unfractionated heparin for up to 48 hours followed by placebo for up to 8 days. Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group. There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux), with significantly fewer cardiac tamponade (48 vs 28) with fondaparinux at 9 days. However, there was no benefit in those undergoing primary percutaneous coronary intervention. 4, 5.

Here one caution is important that fatal bleeding with Fondaparinux can be treated only with supportive treatment. Also half life of Fondaparinux is 17-21 hours. See related previous pearl LMWH and Antidot (protamine). 6

References: (click to get abstrat/article)

1. Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes - Volume 354:1464-1476, NEJM, April 6, 2006
2. Oasis 5 - clinicaltrials.gov
3. Therapy for Patients with Acute Coronary Syndromes - New Opportunities, Volume 354:1524-1527, NEJM April 6, 2006
4. Effects of Fondaparinux on Mortality and Reinfarction in Patients With Acute ST-Segment Elevation Myocardial Infarction - JAMA. 2006;295:1519-1530. Vol. 295 No. 13, April 5, 2006
5. MICHELANGELO OASIS-6 : FOndaparinux in ST Elevation Myocardial Infarction
6. Treatment of postoperative bleeding after fondaparinux with rFVIIa and tranexamic acid. Neth J Med 2005 May;63(5):1846

Prolonged Mechanical Ventilation

Monday April 10, 2006
Prolonged Mechanical Ventilation - Consensus statement of National Association for Medical Direction of Respiratory Care (NAMDRC)


In May 2004, NAMDRC (chair - Neil R. MacIntyre, MD), a physician advocacy organization for excellence in the delivery of respiratory and critical care, made 12 recommendations for patients with Prolonged Mechanical Ventilation (PMV). We are putting only few salient features here. Full article can be obtained from reference.

1. PMV should be defined as the need for more than / = 21 consecutive days of mechanical ventilation for more than / = 6 h/day.

2. In patients with slowly resolving respiratory insufficiency, complete liberation from mechanical ventilation (or a requirement for only nocturnal NIV) for 7 consecutive days should constitute successful weaning.

3. Greatest emphasis should be placed on identifying factors that are potentially reversible, especially iatrogenic factors.

4. All facilities that are available to patients should be screened by the critical care team for effectiveness and safety when effecting discharge for post-ICU weaning.

5. Begin considerations for PMV-focused care when tracheostomy is first considered.

6. PMV weaning strategies should thus incorporate nonphysician-implemented weaning protocols that utilize daily SBTs of progressively increasing duration after a certain level of ventilatory support reduction has occurred.



Reference:
Management of Patients Requiring Prolonged Mechanical Ventilation - Report of a NAMDRC Consensus Conference - Chest. 2005;128:3937-3954.

IV vasotec

Sunday April 9, 2006
Why sometime IV vasotec (enalapril) does not work?


If you are using IV Vasotec to treat hypertension, remember peak effect after the first dose may not occur for up to four hours. But the peak effect of the second and subsequent doses may exceed those of the first. Although in practical world, dose upto 5 mg IV has been prescribed but no dosage regimen has been clearly demonstrated to be more effective in treating hypertension than IV Vasotec 1.25 mg every six hours. Patients with conditions of heart failure, hyponatremia, diuretic therapy, renal dialysis, and volume depletion may drop their blood pressure precipitously and recommended starting dose should be no greater than 0.625 mg.

IV Vasotec should be administrated slowly over 5 minutes.


Reference: Vasotec IV - fda.gov

EGDT and need for PAC

Saturday April 8, 2006
Early Goal-Directed Therapy and Pulmonary Artery Catheter need

Various institutions are running protocols and study in reference to Early Goal-Directed Therapy and we are learning new aspects related to this approach. Recent study from Cooper University Hospital, Camden, NJ (done by Trzeciak, Dellinger, Parillo and Colleauges), found 2 lessons:

1. Emergency medicine and Critical Care collaboration can be run effectively and all end points of EGDT were successfully achieved for 20 of 22 EGDT cases. End points were CVP, MAP and ScvO2.It proved that EGDT can reliably be achieved in "real-world clinical practice". The following median times were observed:

• central line insertion, 1.5 hours;
• CVP goal, 6.0 hours;
• MAP goal, 4.0 hours;
• ScvO2 measured, 2.0 hours; and
• ScvO2 goal, 5.0 hours

2. Another interesting outcome of study was Pulmonary Artery Catheter utilization in the ICU was significantly lower with EGDT (9.1%) vs pre-EGDT (43.8%) [p = 0.01].


Related Previous Pearl:

Shock alert - Shock bed



Reference:
A 1-Year Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency Department - Translating Research to Clinical Practice - Chest. 2006;129:225-232

Permissive Hypercapnia

Friday April 7, 2006
The Bohr Effect and Permissive Hypercapnia

One of the physiologic basis of permissive hypercapnia is to increase unload of oxygen to tissues under decrease PH, call Bohr Effect. The Bohr Effect is an adaptation to release oxygen to the starved tissues in conditions where respiratory carbon dioxide lowers blood pH. When blood pH decreases, the ability of hemoglobin to bind to oxygen decreases, classically said "shifting of oxygen dissociation curve to the right", although the SaO2 may be relatively low. This leads many experts to ask the question - is permissive hypoxemia really bad? 2

In depth, there are many other implications of permissive hypercapnia including suppressive effects on inflammatory mechanisms that may contribute to lung protection with therapeutic hypercapnia. Read informative article implications for permissive and therapeutic hypercapnia (D.A. Kregenow and E.R. Swenson, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA - Reference: Eur Respir J 2002; 20:6-11)



Reference:
1. Respiratory Function of Hemoglobin - Volume 338:239-248, January 22, 1998
2. Permissive Hypoxemia: Is It Time To Change Our Approach? Abdelsalam Chest.2006; 129: 210-211

ScvO2 and SvO2

Thursday April 6, 2006
central venous O2 saturation (ScvO2) or mixed venous O2 saturation (SvO2) ?


Is ScvO2 interchangeable with SvO2 ? The answer is no but the debate is - can they be use independently in the mangement of sepsis ? SvO2 value is usually 5% lower than ScvO2 due to mixing of atrial and coronary sinus blood (and other factors 3). Some experts warn that substituting ScvO2 for Svo2 may produce large errors 1. Dr. Rivers of EGDT- Early Goal Directed Therapy (in which ScvO2 has been used as a mainstay of algorithm) discussed this debate in recent issue of "chest" (march, 2006) 2. And at this point the practice pattern is consist of as he wrote:

"irrespective of whether the ScvO2 value equals the SvO2 value, the presence of a low ScvO2 level in patients with early sepsis portends increased morbidity and mortality"

Present practice target is value of 65% for SvO2 level and 70% for Scvo2 in the resuscitation of patients with severe sepsis. ScvO2 is quick and easy to obtain in comparison to SvO2.



Reference:
1. Lack of Equivalence Between Central and Mixed Venous Oxygen Saturation Chest. 2004;126:1891-1896
2. Mixed vs Central Venous Oxygen Saturation May Be Not Numerically Equal, But Both Are Still Clinically Useful Chest, March 1, 2006; 129(3): 507 - 508
3. Central or Mixed Venous Oxygen Saturation? Kopterides et al. Chest.2005; 128: 1073-1075

How much extra phenytoin

Wednesday April 5, 2006
How much extra phenytoin

The formula to decide, how much extra phenytoin should be prescribed to get level therapeutic is

Extra phenytoin needed = [0.7 x IBW x (15 - current level) ] / 0.92

Where IBW = Ideal body weight (note - this is 'ideal' body weight)


e.g: If patient with ideal body weight of 62 kg has dilantin level of 7.4, the extra required dose would be [0.7 x 62 x (15 - 7.4)] / .92 = 330 mg or to be practical about 300 mg.


Remember this formula is for patient with normal albumin and conserve renal function. Please see pearl from yesterday for phenytoin adjustment with low albumin and low CrCl here


Reference:
Phenytoin dosing guidelines by D.McAuley, GlobalRPh Inc.

Phenytoin level

Tuesday April 4, 2006
Phenytoin (Dilantin) level

The ideal phenytoin level is to have unbound (free) phenytoin level but if free phenytoin level is not available or turn around time is long, it should be adjusted with albumin level with following formula, called Sheiner-Tozer equation. Its not 100% accurate but give good estimate.

Corrected Dilantin = measured level / [ (0.2 x albumin) + 0.1]


e.g: if measured Dilantin level is 8.2 but albumin is 2.2, the corrected Dilantin level would be 8.2 / { (.2 x 2.2) + .1} = 15.2


In renal patients, If patient CrCl is less than 20, use following formula.

Corrected Dilantin = measured level / [ (0.1 x albumin) + 0.1]

e.g: if measured Dilantin level is 8.2 but albumin is 2.2, the corrected Dilantin level would be 8.2 / { (.1 x 2.2) + .1} = 25.6

See the difference ?. Just don't carried away with low level.


Also be cautious, phenytoin's dose increase is not linearly related to serum levels. Small increase in dose may produce disproportionate and actually toxic serum level.

Nesidioblastosis

Monday April 3, 2006
Nesidioblastosis - post gastric bypass complication

Case: 40 years old non-diabetic female, reliable historian, admitted to ICU with life threatening and persistent hypoglycemia. Patient is not on any medication and past medical and surgical history is significant only with gastric bypass surgery 2 years ago. Surgical service decide to take patient to OR.


As gastric bypass procedures are growing in number, Nesidioblastosis (hyperinsulinemic hypoglycemia) is now a documented complication of gastric bypass surgery particularly Roux-en-Y gastric bypass surgery. Patients may present with repeated episodes of profound hypoglycemia which are actually postprandial neuroglycopenia associated with endogenous hyperinsulinemic hypoglycemia. Diagnosis is confirmed by selective arterial calcium-stimulation testing and treatment is partial pancreatectomy. Peri and post-operatively diffuse beta-cell hypertrophy and hyperplasia has been demonstrated (and resected). The exact mechanism is not clear though various explanations has been suggested.


Read very nice review here from Edward E. Mason MD, Ph.D.(University of Iowa health care).


References: (click to get abstract)

1. Gastric Bypass and Nesidioblastosis — Too Much of a Good Thing for Islets? - NEJM , Volume 353:300-302 - July 21, 2005

2. Nesidioblastosis - emedicine.com

Restless Legs syndrome

Sunday April 2, 2006
Restless Legs syndrome

Every now and then, intensivists receive calls regarding issues which are usually not expected from critical care unit. One such instance is Restless legs syndrome. Various pharmacological agents have been described and used with success including benzodiazepines, carbamazepine and clonidine.

In ICU situation, one useful drug in this regard is Ropinirole which is a Dopamine agonist. One of the effect of Ropinirole is heavy sleepiness, which can be use as benefit in ICU. Dose can be initiated from .25 mg PO QHS upto 4 mg PO QHS.



References: (click to get abstract)

1. Restless Legs Syndrome: Detection and Management in Primary Care - NATIONAL HEART, LUNG, AND BLOOD INSTITUTE WORKING GROUP ON RESTLESS LEGS SYNDROME - Vol. 62/No. 1 (July 1, 2000) - American Family Physician.

2. Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebo-controlled study - Mov Disord. 2004 Dec;19(12):1414-23.

Pericardial Effusion on CXR reading

April 1, 2006
Bedside trick ! - To suspect Pericardial Effusion on CXR reading

Pericardial effusion may be difficult to rule out on CXR.

Most patients in ICU have a heart rate of more than 100 bpm. X-ray exposure is usually long enough to allow the heart border to move significantly. If the heart borders are sharply demarcated, consider a pericardial effusion. In other words, in normal CXR you may see little haziness at borders due to movement of heart borders inside pericardium which get lost with pericardial effusion.

Another sign is presence of a thick pericardial fat stripe seen on the lateral view. Please see CXR in this regard here from teaching files of University of Ottawa.