Sunday May 11, 2008
Revisiting basic

Q: According to landmark expert panel conference of 1991/1992, under the auspices of the American College of Chest Physicians and the Society of Critical Care Medicine, what is the widely accepted definition of SIRS (Systemic inflammatory response syndrome) ?



A: SIRS is defined as 2 or more of the following variables:

1. Fever of more than 38°C ( 100.4°F) or less than 36°C ( 96.8°F)
2. Heart rate of more than 90 beats per minute
3. Respiratory rate of more than 20 breaths per minute or a PaCO2 level of less than 32 mm Hg
4. Abnormal white blood cell count (>12,000/µL or <4,000/µl>>10% bands)
   

Editors' note: Objective of above question is to remind the hypocarbia and bandemia part, which are often forgotten. This question is posted here with understanding that there are lot of controversaries surround this defination of SIRS but fortunately or unfortunately, still this is the most accepted criteria in clincal fields.




Reference:

Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:1656-1662

Saturday May 10, 2008
Perfusion site

Comprehensive site for anyone interested to learn and to have resource link available in cardiac anaesthesia and cardiopulmonary bypass.

http://www.perfusion.com.au/CCP/ccp_notes.htm


(Page of Australian & New Zealand College of Perfusionists)

Friday May 9, 2008
Bedside tip - Changing cordis to tripple lumen

This is a regular practice to change cordis (large bore or rapid infuser catheter) to (small bore) central line "over wire", once need for cordis itself is over (like removal of pulmonary artery catheter or need of rapid fluid infusion).

One frequent issue is inability to advance wire in cordis. As cordis is large bore, its 'hub' (see picture below) tends to bend at skin or inside sucutaneous tissue, which prevents advancement of wire. Trick is to retract the cordis about 1-2 cm out of skin, make it straight and advance wire.

Proceed further with usual practice of changing catheters over wire.

Previous related pearls:

Peres Nomogram to calculate required length of central line

Bedside tip - central line removal

Suture at central venous catheter site - a risk ?

Appropriate length of guide wire to advance

Thursday May 8, 2008
ECMO update

Extracorporeal membrane oxygenation (ECMO) refers to the technique of providing both cardiac and respiratory support oxygen to patients by draining blood from the venous system and oxygenating it outside of the body. ECMO uses cardio-pulmonary bypass technology to temporarily provide gas exchange to patients with severe, but potentially reversible, respiratory failure. ECMO is a standard practice in neonatal and pediatric ICUs to support pulmonary failure but remained a very last resort in adult ICUs due to the high technical demands, cost, and risk of bleeding (requires anticoagulation). The major reason ECMO remained unused in adult ICUs is a negative study done about 29 years ago. The National Institutes of Health trial of ECMO in severe acute respiratory failure in 1979 showed mortality in excess of 90% .

ECMO could be a bridge till definite therapy is sought or till healing occurs. Technically, VV or VA (veno-veno or veno-arterial) ECMO can provide sufficient oxygenation for several weeks.

One recent trial called CESAR (Conventional Ventilation or ECMO for Severe Adult Respiratory Failure) showed increase survival among adult patients with severe but potentially reversible respiratory failure compared with conventional ventilatory support.

Data from CESAR trial showed that ECMO may increase the rate of survival without severe disability 6 months after randomization and may be cost-effective compared with conventional ventilatory support.

The conventional treatment group was treated with standard clinical practice, with a low-volume ventilation strategy.

The primary outcome measure was death or severe disability 6 months after randomization and included deaths before hospital discharge if occurring after 6 months.

Severe disability was defined as being both "confined to bed" and "unable to wash or dress oneself."

Patients: A total of 180 patients from 68 centers were randomly assigned to receive

• conventional ventilation (n = 90)
• ECMO (n = 90)

Of the 90 patients assigned to receive ECMO, 22 did not receive ECMO, most often because they improved without it.

A significant number of patients had failure of more than 3 organs in both groups (28 in the ECMO group and 27 in the conventional group).

Results:

• Of the patients randomly assigned to receive ECMO, 57 of 90 met the primary endpoint of survival or absence of severe disability at 6 months compared with 41 of 87 evaluable patients in the conventional ventilation group (survival benefit 63% vs 47%).
• There was also a nonsignificant trend toward decreased deaths before 6 months in the ECMO group vs the conventional ventilation group (57 of 90 vs 47 of 87).
• Patients in the conventional group died more quickly than in the ECMO group (5 vs 15 days). One ECMO-related death occurred, which was attributed to a cannulation problem.
  

Conclusion: The benefit of ECMO was seen regardless of several factors including hospital of trial entry, age, presence of hypoxia, duration of high-pressure ventilation, primary diagnosis at trial entry, and number of organs failed.

Initial data presented by Giles J. Peek, MD, FRCS, from the University of Leicester, Glenfield, United Kingdom, at the Society of Critical Care Medicine 37th Critical Care Congress 2008, Hawaii.

Pre-report details can be read here

Wednesday May 7, 2008
Nebivolol (Bystolic)

Q: How nebivolol (Bystolic), the newly approved beta-blocker, is different from previously approved 18 other beta-blockers?


A: Nebivolol is said to be the 19th beta blocker approved for US market. Nebivolol (Bystolic), is approved by FDA for the treatment of hypertension. The drug is a selective beta 1 blocker but has the added pharmacological properties of producing vasodilation and reducing total peripheral resistance brought about by modulation of nitric-oxide release, rather any receptor blockade.

Coreg (Carvedilol) is another new generation b-blocker which does vasoldilation, but via alpha receptor blocakade.

Because of vasodilatory properties Nebivolol and Coreg have also shown benefit (vs placebo) in heart failure. Unlike Coreg, Nebivolol is not approved for the treatment of heart failure (yet).


Previous related pearls: Regarding Coreg

Tuesday May 6, 2008
DNR Song - funny but so true !

Monday May 5, 2008


Q: What is the drug of choice to control cocaine induced seizures?


A: Diazepam and lorazepam.

Also, barbiturates, may be effective in controlling seizures because they may act synergistically with the benzodiazepines.

Important pearl to remember is: Phenytoin may not be effective against cocaine-induced seizures.

Sunday May 4, 2008

Q: What is the ratio of alpha and beta blockade in Labetalol?



A: As an anti-hypertensive, Labetalol has both alpha-blockade and beta-blockade activity. The ratio of alpha to beta blockade activity is

1:3 when used Orally
1:7 when used intravenously




References:

1. I.V. LABETALOL AND CORONARY ARTERY SURGERY, MOREL et al. Br. J. Anaesth..1984; 56: 664-665

2. Comparative study of esmolol and labetalol to attenuate haemodynamic responses after electroconvulsive therapy - Kathmandu University Medical Journal (2007), Vol. 5, No. 3, Issue 19, 318-323, pdf file

Saturday May 3, 2008
Steroids in sepsis controversy - what 'Guru' thinks !

Here is a very well rounded commentary on steroids in sepsis from internationally famed Critical Care master Dr. Jean-Louis Vincent. We are just posting important points from commentary due to space constrain. You can read full text with references by clicking at link below:

"............Forty years ago, high-dose steroids were used in the belief that, because sepsis is an inflammatory response, the anti-inflammatory properties of steroids could be useful. Initial studies were encouraging, with Schumer demonstrating that treatment with one or two doses of intravenous dexamethasone (3 mg/kg) or methylprednisolone (30 mg/kg) was associated with reduced mortality compared with saline treatment in patients with septic shock. Two large, double-blind, randomized controlled trials later failed to confirm these findings, however, and two meta-analyses in the mid 1990s concluded that steroids were ineffective or indeed were potentially harmful in sepsis.

Then, in the late 1990s, several studies were published suggesting a role for much smaller, so-called stress, doses of steroids in reducing vasopressor requirements in patients with septic shock. These results led to a study by Annane and colleagues in which patients with relative adrenal insufficiency – as assessed by nonresponse to a corticotropin test – who were treated with hydrocortisone (50 mg intravenously every 6 hours) and fludrocortisone (50 μg orally daily) for 7 days had a reduced mortality compared with nonresponders treated with placebo. Despite concerns regarding the lack of statistical significance in overall mortality rates at 28 days, the results from this study led to steroids being recommended in the treatment of patients with septic shock. Steroid use was also incorporated into the so-called sepsis bundles, with the recommendation that all patients with septic shock should receive low-dose corticosteroids within 24 hours of diagnosis.

Doubts remained, however, and a large, international, multicenter study was conducted to confirm the results of the earlier study. The Corticus – Corticosteroid Therapy of Septic Shock – study, which included close to 500 patients, recently showed that hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not respond to a corticotropin test. The results from the Corticus study were somewhat disappointing, and, in the accompanying editorial, Dr Finfer suggested the need for a further study to explore the effects of steroids in septic shock in a much larger population. With no signal from the Corticus study, however, merely increasing the size of the study is unlikely to show mortality differences.

Importantly, apart from the differences in effects on outcome, there were other notable differences between the Corticus study and Annane and colleagues' study, including the larger number of postoperative patients, the more common abdominal source of the sepsis, and, in particular, the lower severity of illness in the Corticus study. This latter factor is particularly important and can be explained by the fact that many patients with severe septic shock were treated with steroids in accordance with guidelines current at the time of the study, and hence were excluded from enrollment – so the included population, by definition, consisted of less severely ill patients. As a result of this lower severity of illness, the mortality rate in the Corticus study was about one-half that of Annane and colleagues' study. It is therefore still possible that steroids may decrease mortality in very ill patients, just not in those with moderately severe shock.
Similar observations were made with activated protein C, another adjunct therapy for sepsis, which was shown to reduce mortality in very ill patients but not in those patients with a lower risk of death. I believe we do need another trial of steroids in sepsis, but specifically in patients with severe septic shock rather than just in a larger general population of septic shock patients.

...................Perhaps the time has come to take a step back and reflect on past efforts so that future clinical trials will be conducted in an optimal manner to limit the pendulum effect and to provide results that stand up to scrutiny and can be immediately introduced into clinical practice to the benefit of our patients."


Reference: Steroids in sepsis: another swing of the pendulum in our clinical trials, Jean-Louis Vincent, Department of Intensive Care, Université libre de Bruxelles, Erasme Hospital, Brussels, Belgium, Critical Care 2008, 12:141

Friday May 2, 2008
Digoxin recall !!

A class I recall is being issued on all Digitek (digoxin) tablets, which may contain twice the approved level of digoxin.

Digitek is a registered trademark of Actavis Totowa (formerly Amide Pharmaceutical, Inc.) for their digoxin tablets. The drug is distributed by Mylan Pharmaceuticals Inc., under a “Bertek” label and by UDL Laboratories, Inc. under a “UDL” label.

See FDA press release here


Previous related pearls on "Dig."

Treating Digoxin toxicity 1

Treating Digoxin Toxicity 2

What Dig. level makes you happy?

Adenosine and Digoxin !

Thursday May 1, 2008
Conivaptan's (Vaprisol) drug interactions
Q: Conivaptan (Vaprisol), a Vasopressin Antagonist, which is indicated for the management of euvolemic hyponatremia - can increase the concentration of following drugs if use concomittently? (choose one)

A) Amlodipine (Norvasc)
B) Simvastatin (Zocor)
C) Digoxin (Lanoxin)
D) Midazolam (Versed)
E) All of the above


Answer is E: All of the above

Administration of oral conivaptan 40 mg twice daily with amlodipine besylate (Norvasc) resulted in a two-fold increase in the AUC concentration and increased half-life of amlodipine.

The combined use of IV conivaptan and midazolam should be avoided, because the AUC concentration of midazolam may be increased by two-fold to three-fold when these agents are used together.

The coadministration of conivaptan and HMG-CoA reductase inhibitors (statins) such as simvastatin (Zocor) should also be avoided because the AUC concentration of the statin is increased by three-fold.

Digoxin when taken with oral conivaptan, results in a 30% reduction in clearance of digoxin.


Read nice review on Conivaptan
(reference: P&T • March 2007 • Vol. 32 No. 3, Page 140)