REMI 2152. Eficacia y seguridad de la procalcitonina para guiar la retirada de los antibióticos en la UCI

ARTÍCULO ORIGINAL: Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE, Loef BG, Dormans T, van Melsen GC, Kluiters YC, Kemperman H, van den Elsen MJ, Schouten JA, Streefkerk JO, Krabbe HG, Kieft H, Kluge GH, van Dam VC, van Pelt J, Bormans L, Otten MB, Reidinga AC, Endeman H, Twisk JW, van de Garde EM, de Smet AM, Kesecioglu J, Girbes AR, Nijsten MW, de Lange DW. Lancet Infect Dis. 2016 Jul;16(7):819-27.[Resumen] [Artículos relacionados]

INTRODUCCIÓN: Algunos estudios previos han mostrado que los niveles de procalcitonina pueden ser una guía útil para reducir la duración de la antibioterapia en los pacientes críticos. Sin embargo, la seguridad de los protocolos basados en este marcador no ha sido aún bien establecida y en uno de esos estudios, el PRORATA, se observó una tendencia a una mayor mortalidad en los pacientes tratados con uno de esos protocolos. El objetivo de este nuevo estudio fue valorar la seguridad de un protocolo de guía de la antibioterapia basado en la procalcitonina en pacientes adultos ingresados en UCI.

RESUMEN: Se trata de un ensayo clínico multicéntrico, aleatorizado, no enmascarado. Los pacientes fueron asignados a un protocolo basado en la procalcitonina para decidir la interrupción de la antibioterapia (761) o al protocolo habitual (785). En el grupo de la procalcitonina la suspensión de la antibioterapia se recomendó cuando sus niveles decrecieron a un 80% de su valor pico o cuando fueron de  0,5 μg/L. El desenlace principal fue el consumo de antibióticos (expresado como dosis definida diaria, DDD) y la duración del tratamiento. Los desenlaces principal de seguridad fueron la mortalidad a los 28 días y al año. Entre los desenlaces secundarios, se estudiaron la duración de la estancia en la UCI y en el hospital. En el 71% de los pacientes asignados al grupo de la procalcitonina, los antibióticos fueron interrumpidos durante su estancia en la UCI.

La mediana del consumo de antibióticos fue de 7,5 DDD (IRQ de4,0 – 12,7) en el grupo guiado por la procalcitonina y de 9,3 DDD (IRQ de 5,0 – 16,6)  en el grupo de control (diferencia absoluta entre ambos grupos de 2,69; 95% del IC de 1,26 – 4,12; P < 0,0001. La mediana de la duración del tratamiento fue de 5 días (IRQ de 3 – 9) en el grupo guiado por la procalcitonina y de 7 (4 -11) en el grupo de control (diferencia de 1,22; 95% del IC de 0,65 – 1,78; P < 0,0001). La mortalidad a los 28 días fue inferior en el grupo de la procalcitonina  en el análisis por intención de tratar (diferencia absoluta de 5,4%; 95% del IC de 1,2 – 9,5; P =0,0122). La diferencia seguía siendo significativa al año.

COMENTARIO: El estudio ha sido financiado por la empresa fabricante del método de detección de la procalcitonina. Como en otros estudios, en más de la mitad de lo pacientes asignados a la procalcitonina, no se cumplió en protocolo. El hallazgo sobre la mortalidad es inesperado y puede deberse a una detección más rápida de las reinfecciones o la falta de adherencia al protocolo en los casos más dudosos. Por todo ello, la utilidad real de la procalcitonina sigue sin estar definida.


Ramón Díaz-Alersi
Hospital U. Puerto Real, Cádiz.
© REMI, http://medicina-intensiva.com. Agosto 2016.

ENLACES:

  1. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Régnier B, Brun-Buisson C, Chastre J, Wolff M; PRORATA trial group. Lancet. 2010 Feb 6;375(9713):463-74.  [PubMed] [REMI]
  2. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. A randomized controlled trial. Shehabi Y, Sterba M, Garrett PM, Rachakonda KS, Stephens D, Harrigan P, Walker A, Bailey MJ, Johnson B, Millis D, Ding G, Peake S, Wong H, Thomas J, Smith K, Forbes L, Hardie M, Micallef S, Fraser JF; ProGUARD Study Investigators; ANZICS Clinical Trials Group. Am J Respir Crit Care Med. 2014 Nov 15;190(10):1102-10.  [PubMed] [REMI]


BÚSQUEDA EN PUBMED:
  • Enunciado: estudios sobre antibioterapia guiada por la procalcitonina
  • Sintaxis: procalcitonin-guided antibiotic therapy 
  • [Resultados]
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Drug Rashes: Not always so simple…

Author: Summer Chavez, DO, MPH (EM Resident Physician, Virginia Tech-Carilion) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC)

A few days ago, you discharged a well-appearing, 82-year-old female with antibiotics for a symptomatic UTI. At your shift today, you recognize her name and wonder why she has returned back to the ED. When you see the patient, she looks much worse, with a fever and rash all over her arms and chest. What’s going on here? Could this be a drug rash?

Morbilliform Drug Eruptions

Approximately 90-95% of all drug rashes are “drug-induced exanthems”, also referred to as morbilliform or maculopapular drug eruptions1,2. These rashes are defined by widespread erythematous macules or papules that appear about a week or two after starting the triggering drug, with antibiotics as the most common culprits. For those who have been sensitized in the past, the rash appears even earlier, such as two days2. In most severe forms, mucous membranes, hair, and nails are involved2, though this is rare. How does this even come about? To answer that question, we’ll need to take a quick trip back to memory lane and revisit medical school immunology. While the exact pathogenesis of Type IV hypersensitivity reactions still isn’t completely known, all you need to know is that T-cells recognize a portion of the drug as an antigen, which ramps up an immune response, and it takes at least a few days for this to occur.

Some people are more likely than others to have severe drug reactions, based on their HLA make-up2. Other risk factors include immune suppression, concurrent viral infection or multiple medications simultaneously2. This class of rashes gets its name because they look similar to viral rashes. Remember, it’s very uncommon for the mucosa or face to be involved or for systemic symptoms (i.e. fever, facial swelling, blistering), so if that’s the case with your patient, start thinking about DRESS, SJS, and TEN2Forty-eight hours after stopping the drug, symptoms will usually peak and then resolve in about one to two weeks2. A sign that the patient is improving is desquamation2.

Screen Shot 2016-08-21 at 8.36.55 PMThe big key to diagnosing a morbilliform drug reaction is getting a good history from the patient. Keep in mind that anti-seizure medications, allopurinol and antibiotics can take up three weeks to manifest with a rash2. Consider getting a CBC with differential to look for eosinophilia (DRESS) and LFTs and creatinine to look for systemic involvement (SJS/TEN, DRESS)2. Skin biopsies typically are not used unless you have a high suspicion for one of the severe types of drug rashes2.

Screen Shot 2016-08-21 at 8.37.17 PM
After identifying the drug and discontinuing it, the immediate management in the ED involves symptomatic treatment. There are no randomized clinical trials evaluating certain treatments over others, but some authors suggest avoiding systemic steroids with the possible exception for those patients with systemic involvement2.  Currently, the mainstay of treatment is high-potency topical steroids and oral antihistamines2. There may be certain instances where the concept of “treating-through” is utilized – such as a patient with HIV with no other alternative medications available2.

Erythema Multiforme

This condition starts off as symmetric macules on the trunk and extremities that develop into a target-like lesion3. Bulla may form, and mucus membranes are sometimes involved3. The rash usually lasts from 1 week to about a month3. While the strongest association is with HSV infection, either primary or recurrent, less than 10% of cases are associated with drugs – typically NSAIDs, antibiotics, sulfa drugs, and anti-epileptics3. The mainstay of treatment is preventing herpes outbreaks3. Systemic steroids should be avoided3. While patients with classic presentations can most likely be discharged home, those with atypical presentations or systemic involvement should be evaluated by a dermatologist and may need admission3.

 

Drug Rash with Eosinophilia and Systemic Symptoms Syndrome (DRESS)

DREScreen Shot 2016-08-21 at 8.37.28 PMSS is a side effect of taking a new medication that usually happens within 2 months of the first dose4. Although more commonly seen in anticonvulsants and sulfa medications, antibiotics, CCB, NSAIDs, and anti-retrovirals have also been linked to DRESS4. The earliest signs may be fever and rash4. In order to be classified as DRESS, there must be organ involvement, usually hepatic or renal4. About one third of patients will also have an eosinophilia4. Treatment in the ED involves stopping the medication and  supportive care with antipyretics and antipruitics4. Disposition for these patients with suspected DRESS typically involves admission4.

 

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

Screen Shot 2016-08-21 at 8.37.42 PMSJS and TEN are diseases on the same spectrum, differing in severity5. SJS involves less than 10% of the skin surface, while TEN affects more than 30% of the skin surface5. There is an area of overlap between these two markers5. Although SJS/TEN can be drug-induced, it can also be idiopathic5. These rashes are thought to be caused by diffuse death of keratinocytes caused by a cell-mediated cytotoxic effect5. Confluent macules and target lesions merge into flaccid blisters, with majority of involvement on the trunk, arms ,and legs. Mucous membranes are also involved5. In 80% of cases of TEN, there is a strong correlation to a drug5. Drugs with a higher risk of TEN include allopurinol, sulfa drugs, anti-epileptics, nevi rapine  and oxicam NSAIDs6. When the blisters spread with pressure, it’s called positive Nikolsky sign5. Close to 85% of patients will have conjunctival involvement5.

Screen Shot 2016-08-21 at 8.37.54 PMOther findings including tachycardia, tubular necrosis, and erosions of the respiratory and GI tracts5. Resuscitation in the ED includes fluids and electrolyte replacement, but steroids and IV immunoglobulins remain controversial5. Debridement is not recommended5. For ocular involvement, erythromycin ointment can be used5. Patients should be admitted to at least a step down unit, if not an ICU5.

 

 

Drug-Specific Rashes

  • Warfarin-Induced Cutaneous Necrosis: Usually occurs between the third and fifth day of startinganticoagulation. The kind of rash can be almost anything and usually shows in areas of excess subcutaneous fat7.

Screen Shot 2016-08-21 at 8.38.09 PM

  • Heparin-Induced Cutaneous Necrosis: Occurs typically at the injection site7.Screen Shot 2016-08-21 at 8.38.35 PM

All pictures from Access Emergency Medicine, Tintinalli’s 8th ed.

Summary:

  • Most (90%) drug rashes are morbilliform drug eruptions. Treat symptomatically with topical steroids and oral antihistamines.
  • Patients with DRESS will have hepatic or renal involvement, usually eosinophilia and are treated with antipyretics and antipruritics.
  • SJS/TEN involve mucous membranes and are a life-threatening rash not to miss!

 

References / Further Reading:

  1. Samuel A, Chu C-Y. Drug eruptions [Internet]. In: Dellavalle R, Mockenhaupt M, Roujeau J-C, Corona R, editors. UpToDate. 2016. Available from: http://www.uptodate.com/contents/drug-eruptions?source=search_result&search=Drug+eruptions&selectedTitle=1~150#
  2. Bircher A. Exanthematous (morbiliform) drug eruption [Internet]. In: Mockenhaupt M, Roujeau J-C, Corona R, editors. UpToDate. 2016. Available from: http://www.uptodate.com/contents/exanthematous-morbilliform-drug-eruption?source=search_result&search=Exanthematous+%28morbilliform%29+drug+eruption&selectedTitle=1~124
  3. Hardin JM. Chapter 13. Cutaneous Conditions [Internet]. In: Knoop KJ, Stack LB, Storrow AB, Thurman RJ, editors. The Atlas of Emergency Medicine, 3e. New York, NY: The McGraw-Hill Companies; 2010 [cited 2016 Jun 28]. Available from: http://mhmedical.com/content.aspx?aid=6003676
  4. Sochor M, Pandit A, Brady WJ. Generalized Skin Disorders [Internet]. In: Tintinalli JE, Stapczynski JS, Ma OJ, Yealy DM, Meckler GD, Cline DM, editors. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. New York, NY: McGraw-Hill Education; 2016 [cited 2016 Jun 17]. Available from: http://mhmedical.com/content.aspx?aid=1121515645
  5. Wolff K, Johnson RA, Saavedra AP. Severe and Life-Threatening Skin Eruptions in the Acutely Ill Patient [Internet]. In: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 7e. New York, NY: McGraw-Hill Education; 2013 [cited 2016 Jul 3]. Available from: http://mhmedical.com/content.aspx?aid=1123465964
  6. Valeyrie-Allanore L, Roujeau J-C. Medications and the Risk of Toxic Epidermal Necrolysis. In: Wolff K, Goldsmith L, Katz S, Paller A, Leffell D, editors. Fitzpatrick’s Dermatology in General Medicine. McGraw Hill; p. Epidermal Necrolysis.
  7. Wolff K, Johnson RA, Saavedra AP. Adverse Cutaneous Drug Reactions [Internet]. In: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 7e. New York, NY: McGraw-Hill Education; 2013 [cited 2016 Jul 3]. Available from: http://mhmedical.com/content.aspx?aid=1123469219
  8. Wolff K, Johnson RA, Saavedra AP. Exanthematous drug eruption: ampicillin [Internet]. In: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. McGraw-Hill Education; Available from: www.accessmedicine.com

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EMJ Blog – Should More Emergency Physicians be ‘Piloting British Airways’? – The Musings of a Trainee

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I’ve written a second piece for the Emergency Medicine Journal Blog which I’m very excited about.

The post tackles a fairly controversial issue in the UK – the role of EM doctors in emergency airway management. The ‘ED-RSI’ landscape over here is very different to Australia and the US, and my hope is that the piece will stimulate some positive discussion, and hopefully contribute to some overdue culture-change in British hospitals.

The post was published on the blog earlier today, check it out by clicking here.

I hope you enjoy!

Robert Lloyd
@PonderingEM

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Futureproofing EM: Why your trainees deserve it (and your nation needs it). St.Emlyn’s

St.Emlyn's - Meducation in Virchester #FOAMed

I suspect all Deaneries (locality branches of Health Education England as they are now known) have their traditions and meetings. In the former NW post-graduate deanery we have ours. One of these is Calman day. Until this year it was...
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The post Futureproofing EM: Why your trainees deserve it (and your nation needs it). St.Emlyn’s appeared first on St.Emlyn's.

I hate Mondays!

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Garfield had it right. Mondays are the worst. 

Want proof? Well, in 2004 the CDC published a survey measuring health care utilization among US Emergency Departments over a 10 year period.

The results? ED visits peaked on Monday and then decline throughout the week, and Medicare patients were more likely to visit the ED on a Monday than any other day.

Want more depressing data? There was an average of 39 visits per 100 persons, and for patients over 75 years of age – there was an average of 61 visits per 100 persons. (Good luck if you’re in Geri today!)

If you have free time (which you wont) check out the full survey here. There are all sorts of fascinating statistics to justify your grumpy attitude! Additional data on ED overusage can be found here, courtesy of your friends at the CDC.

References:

McCaig, Linda F., and Eric W. Nawar. National hospital ambulatory medical care survey: 2004 emergency department summary. No. 372. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, 2006.