Saturday February 16, 2008
Synergistic agents for Daptomycin

Daptomycin is the first approved member of a new class of antibiotics, namely the cyclic lipopeptides. Daptomycin has rapid bactericidal activity against Gram-positive pathogens.

Daptomycin was shown to be not inferior to antimicrobial standard therapy for Staphylococcus aureus bacteremia and right-sided endocarditis.

This is of interest to know that there is a marked synergy between daptomycin and both rifampin and ampicillin against vancomycin-resistant enterococci (VRE) - despite high-level of ampicillin resistance alone. Also most strains of MRSA are found to have synergism between daptomycin and oxacillin despite it shows resistant alone to oxacillin (as in case of ampicillin in VRE). Ampicillin-sulbactam, ticarcillin-clavulanate, or piperacillin-tazobactam showed synergy comparable to or greater than daptomycin with oxacillin.

It may be of clinical benefit to add synergistic agents while using Daptomycin as it is a 'concentration-dependent' drug.



References: click to get abstract/articles

1. Synergy of Daptomycin with Oxacillin and Other ß-Lactams against Methicillin-Resistant Staphylococcus aureus Antimicrobial Agents and Chemotherapy, August 2004, p. 2871-2875, Vol. 48, No. 8

2. Daptomycin: A Review 4 Years after First Approval Pharmacology 2008;81:79-91

Friday February 15, 2008
THAM


Introduction; In patients with acute respiratory distress syndrome (ARDS), permissive hypercapnia is a strategy to decrease airway pressures to prevent ventilator-induced lung damage by lowering tidal volumes and tolerating higher arterial carbon dioxide tension. A pure respiratory acidosis generally does not require alkali therapy. Alkali therapy is indicated for either a metabolic acidosis or a mixed acidosis. The choice of buffer is based on type of acidosis, cardiorespiratory status, and lung mechanics.

Problem with NaHCO3: Slow infusions of NaHCO3 can be used to treat non-anion gap metabolic acidosis and some forms of increased anion gap acidosis. But using NaHCO3 to treat type A (hypoxia-related) lactic acidosis can be hazardous, particularly under conditions of hypoxemia, inadequate circulation, and limited alveolar ventilation.

THAM: Under above circumstances, THAM is the preferable buffer because it does not increase PaCO2 and is excreted by the kidneys. Tromethamine (THAM) is a sodium-free alkalinizing agent that acts as a hydrogen ion (proton) acceptor. It is a weak base that combines with hydrogen ions from carbonic acid to form bicarbonate and cationic buffer. Administration of tromethamine decreases hydrogen ion concentration, which results in a decrease in carbon dioxide concentrations and an increase in bicarbonate concentrations. The administration of Tham also increases urine output through osmotic diuresis. Excretion of electrolytes and CO2 is also increased. Urine pH is raised along with the excretion of electrolytes.

Usual Dose:

Dose in ml's of 0.3M THAM = (1.1) (Wt. in Kg) (normal HCO3 – Pt’s HCO3)

OR

Dose in ml’s of 0.3M THAM = body wt in kg X base deficit in MEq/L x 1.1


Total dose should be administered over a period not less than 1 hour via central line..3M THAM solution is available as premix and is contra-indicated in renal failure, anuria and hyperkalemia. It may cause transient hypoglycemia and respiratory depression.

Thursday February 14, 2008
Alinia(Nitazoxanide) in Clostridium Difficile Colitis

Beside Vancomycin and Flagyl, an adjuvant treatment may be use in C. diff. Colitis with Alinia (Nitazoxanide), 500 mg twice daily. Actually, emerging literature is showing it to be a promising treatment in cases where metronidazole fails to eradicate C.diff.

Nitazoxanide is an FDA approved drug to treat parasitic diseases of the gastrointestinal tract. It is very widely use as an antiprotozoal agent in pediatric patients with diarrhea. The drug acts by blocking and interfering with anaerobic metabolic pathways, and has been shown to have excellent activity against C. difficile. Limited but postive literature shows its value in C.dif. colitis both as an adjuvant as well as in metronidazole failed C.diff. colitis.




References: click to get abstract/article

1. Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide, Journal of Antimicrobial Chemotherapy 2007 59(4):705-710

2. Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Infection - clinicaltrials.gov

3. In Vitro and In Vivo Activities of Nitazoxanide against Clostridium difficile - Antimicrob Agents Chemother. 2000 September; 44(9): 2254–2258.

4. Nitazoxanide for the treatment of Clostridium difficile colitis. , Clin Infect Dis. 2006 Aug 15;43 (4):421-7 16838229

Wednesday February 13, 2008

Q; Name few drugs which can be use in VRE (Vancomycin-resistant enterococcus) Meningitis ?


A; New growing literature is showing that IV and even PO Zyvox (linezolid) should be the first line of treatment in VRE Meningitis as it has a very good penetration in CSF.

Other viable choices are chloramphenicol, Ampicillin (or penicillin) and Synercid (Quinupristin/dalfopristin).





Reference: click to get abstract/article

1. Successful treatment of vancomycin-resistant enterococcus meningitis with linezolid: Case report and review of the literature Critical Care Medicine. 29(12):2383-2385, December 2001.

Tuesday February 12, 2008
Precedex® (dextromedetomidine) - better?

Precedex is now a commonly used drip in ICUs due to its simultaneous anxiolytic, anesthetic, hypnotic, and analgesic properties and moreover it does not depress respiration. But still cost is a major concern to prescribe this medicine.

A recent study published in JAMA 1 found Dexmedetomidine superior to Lorazepam for sedation. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction. Interestingly, there was no difference in cost.

Design: It was a double-blind, randomized controlled trial.

Number: 106 adult mechanically ventilated medical and surgical ICU patients. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours.

Scales used:

• Richmond Agitation-Sedation Scale (RASS).
• Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU).

Results :

• Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0)
• a lower prevalence of coma (63% vs 92%)
• Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%)
• The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group
• cost of care was similar between groups
• The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group

Conclusion: In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion.


Related previous pearl: Regarding Dexmedetomidine (Precedex)




Reference: click to get abstract/article

1. Effect of Sedation With Dexmedetomidine vs Lorazepam on Acute Brain Dysfunction in Mechanically Ventilated Patients , The MENDS Randomized Controlled Trial, JAMA. 2007;298(22):2644-2653.

Monday February 11, 2008
LMA insertion - an excellent animation video

This video is included in our video section

Sunday February 10, 2008
Venous PH


Q: During or immediately following CPR, and in hemodynamic shock which PH is more worthwhile to follow ?


A: Venous PH

During shock state, venous blood is a more accurate reflection of metabolism in tissues. It may be of benefit to follow the trend in venous PH to measure the improvement of shock following CPR and hemodynamic instability.



Reference: click to get abstract/article

Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation, NEJM, Number 3, Volume 315:153-156, July 17, 1986

Saturday February 9, 2008
Adjuvant treatment in Ethylene Glycol toxicity


Q: Which 2 very easily available and cost-effective drugs should be added as an adjuvant treatment in Ethylene Glycol toxicity (though mostly forgotten) ?



A: Thiamine 100 mg IV daily and Pyridoxine 100 mg IV daily

One of the metabolite of Ethylene Glycol is Glycolic acid which converts into Glycoxylic Acid and remains toxic. Thiamine and Pyridoxine converts Glycoxylic Acid into non-toxic metabolites and decreases long term toxic effects of Ethylene Glycol.


Related previous pearl:

Ethanol drip in Ethylene Glycol toxicity

Treating Ethylene Glycol poisoning

Friday February 8, 2008
Dialysis and central catheter's diameter !

Internal diameter of each lumen of dialysis catheter is about twice the diameter of each lumen in a triple-lumen central venous catheter.

Clinical application: As per Hagen-Poiseuille equation, just 2 fold increase in radius increase flow by 16 fold.

Thursday February 7, 2008
Sodium Bicarbonate in contrast induced nephropathy (CIN) - a risk ?


Sodium Bicarbonate is increasingly being used to prevent contrast induced nephropathy which was based on a small study (1). The role of this prophylaxis is being questioned by a recent large retrospective study from Mayo (2).

Groups:

1. sodium bicarbonate,
2. N-acetylcysteine, and
3. the combination of sodium bicarbonate with N-acetylcysteine

Contrast nephropathy was defined as postexposure creatinine elevation of 25% or >0.5 mg/dl within 7 days of contrast exposure.

Total numbers:

• A total of 11,516 contrast exposures in 7977 patients had creatinine values available for review before and after contrast exposure.
• Sodium bicarbonate was used in 268 cases,
• N-acetylcysteine was used in 616 cases, and
• both agents were used in combination in 221 cases
  

Results:

• Use of sodium bicarbonate alone was associated with an increased risk of contrast nephropathy compared with no treatment
• N-acetylcysteine alone and in combination with sodium bicarbonate was not associated with any significant difference in the incidence of contrast nephropathy.
  
  

Conclusions: The use of intravenous sodium bicarbonate was associated with increased incidence of contrast nephropathy.

But also note, recent REMEDIAL trial, showed that the strategy of volume supplementation by sodium bicarbonate plus NAC seems to be superior to the combination of normal saline with NAC in preventing CIN in patients at medium to high risk. (3)


Editors' note: So far, it appears except for adequate hydration, most of the therapies have no consistent track of advantage and results are variable.

References: click to get abstract/article

1. Prevention of contrast-induced nephropathy with sodium bicarbonate: A randomized controlled trial. JAMA 2004; 291:2328-2334.

2. Sodium bicarbonate is associated with an increased incidence of contrast nephropathy: A retrospective cohort study of 7977 patients at Mayo Clinic. Clin J Am Soc Nephrol 2008; 3:10-18.

3. Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL). A randomized comparison of 3 preventive strategies. Circulation 2007; DOI:10.1161/CIRCULATIONAHA.106.687152.

Wednesday February 6, 2008



Case: 52 year old male is back from cardiac angioplasty with abciximab (ReoPro) infusion. Pre-cath labs were normal. CBC was send per protocol after 4 hours of abciximab infusion and lab call with critical platelet level of 62. Abciximab was stopped and hematology consulted. Hematology advised to restart abciximab !!


Pseudothrombocytopenia

Pseudothrombocytopenia is a common phenomenon with patients on abciximab (ReoPro). It is a benign condition and is not a real thrombocytopenia as platelets actually clump in collecting tubes containg EDTA. It is an important diagnosis to make. Diagnosis can be made by reviewing peripheral blood film or drawing blood in citrated or heparinized tube. It is not clear why abciximab cause more EDTA-induced platelet clumping.* EDTA (Ethylenediaminetetraacetic acid) is a commonly used anticoagulant in sampling tubes for blood counts.



References: click to get abstract/article

1. Occurrence and clinical significance of pseudothrombocytopenia during abciximab therapy J Am Coll Cardiol. 2000 Jul;36(1):75-83.
2. Abciximab-Associated Pseudothrombocytopenia - Circulation. 2000;101:938
3. EDTA dependent pseudothrombocytopenia caused by antibodies against the cytoadhesive receptor of platelet gpIIB-IIIA - Journal of Clinical Pathology 1994;
47:625-6304. Pseudothrombocytopenia Volume 329:1467 Nov. 11, 1993

Tuesday February 5, 2008


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

A: Yes, it can be precipitate 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 glucose drip in patients who are at risk of Wernicke's Encephalopathy. Disorder was described 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 at emedicine.com

Monday February 4, 2008
What to do in case of accidental esophageal intubation !

Editors' note: The following video is a practice or opinion of some intensivits but not proved or recommended by clinical trials.

Total video time: 1 minute 24 secs

Sunday February 3, 2008
Bimanual Laryngoscopy - BURP !!

One 'trick' to enhance successful intubation is using 'Bimanual Laryngoscopy'.
Its different from cricoid pressure as explained in video.

Its also called BURP: pressure backwards,upwards and to the right.





source:

Airwaycam.com

Saturday February 2, 2008
Arterial line colonization and infection

In this month of Critical Care Medicine 1, a study published from australia: Prospective study of peripheral arterial catheter infection and comparison with concurrently sited central venous catheters. It was prospective 24-month cohort study. 331 arterial catheters were observed for 1,082 catheter days, and 618 central venous catheters for 4,040 catheter days.

All catheters were inserted by trained personnel under aseptic conditions, and management was standardized.

Results:

• The incidence per 1,000 catheter days of catheter-related bloodstream infection was 0.92 for arterial catheters and 2.23 for central venous catheters.
• Arterial catheter colonization was not significantly different than that in central venous catheters.
• Femoral arterial catheters were colonized more often than radial arterial catheters
• Colonization was significantly higher when the catheter was inserted in the operating theater or emergency department compared with the ICU !

Conclusions: The incidence of catheter-related bloodstream infection from arterial catheters was low. However, both arterial catheter colonization and rates of catheter-related bloodstream infection were similar to those in concurrently sited and identically managed central venous catheters. By inference, the arterial catheter should be accorded the same degree of importance as the central venous catheter as a potential source of sepsis.

Reference: click to get abstract

Prospective study of peripheral arterial catheter infection and comparison with concurrently sited central venous catheters - Critical Care Medicine. 36(2):397-402, February 2008.

Friday February 1, 2008
Procedure video - IJ central line under ultrasound

Related previous video: Ultrasound windows for venous catheter placement