Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Ubiquitous steroid use in the intensive care unit
- Amit Patel (22 October 2008)
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Prophylactic steroids to prevent ‘extubation failure’ in ventilated children
- Joseph L Mathew, Chandigarh, India 160012 (26 October 2008)
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Corticosteroids pharmacodynamics explains late effects and may be critical to optimize therapeutic outcomes.
- Fernando Martins do Vale (10 November 2008)
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Major post extubation stridor in ICU is not common
- Cecily M D Don, Jonathan P Aldridge, Consultant, Anaesthesia & Intensive Care Medicine, Borders General Hospital, Melrose TD6 9BS. (17 November 2008)
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Post extubation laryngeal oedema in anesthesia for surgical adult patients
- Mohamad Said Maani Takrouri, Omer Talab, Consultant Ahsan Zafrullah Consultant Sabry Radwan Assistant Consultant (4 January 2009)
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Post extubation laryngeal oedema in anesthesia for surgical adult patients
- Mohamad Said Maani Takrouri, Omer Talab, Consultant Ahsan Zafrullah Consultant . Sabry Radwan Assistant Consultant (5 January 2009)
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It’s the 30th birthday of ‘Evidence Based Medicine’ and time to meet Cochrane’s Challenge.
- Tony K Chow, Victoria, Australia 3128 (21 January 2009)
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Amit Patel, NIHR Academic Clinical Fellow Imperial College London, Hammersmith Hospital, Du Cane Rd, London, W12 0NN
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The six eligible trials analysed in this updated meta-analysis of prophylactic parenteral steroid use to prevent laryngeal oedema after extubation, and subsequent reintubation,[1] included protocols with different agents and doses, which are not equivalent. Their biological half-lives also vary considerably, with hydrocortisone being the shortest, methylprednisolone intermediate and dexamethasone the longest acting (36- 54 hours). Reduced laryngeal oedema is most likely related to corticosteroid rather than mineralocorticoid activity. The list below shows how these studies were also different regarding their equivalent dexamethasone dose, which mainly has corticosteroid effect. Study: Gaussorgues; 1987; France and multicentre. Steroid dose: 40 mg IV methylprednisolone. Dexamethasone equivalent dose: 7.5 mg Total Dexamethasone equivalent dose: 30 mg Study: Darmon; 1992; France and multicentre Steroid dose: 8 mg IV dexamethasone Dexamethasone equivalent dose: 8 mg Total Dexamethasone equivalent dose: 8 mg Study: Ho; 1996; Taiwan. Steroid dose: 100 mg IV hydrocortisone. Dexamethasone equivalent dose: 3.75 mg. Total Dexamethasone equivalent dose: 3.75 mg. Study: Cheng; 2006; Taiwan. Steroid dose: 40 mg IV methylprednisolone. Dexamethasone equivalent dose: 7.5 mg. Total Dexamethasone equivalent dose: 30 mg (4 injection group); 7.5 mg (1 injection group). Study: Francois; 2007; France and multicentre. Steroid dose: 20 mg IV methylprednisolone Dexamethasone equivalent dose: 3.75 mg Total Dexamethasone equivalent dose: 15 mg Study: Lee; 2007; Taiwan. Steroid dose: 5 mg IV dexamethasone. Dexamethasone equivalent dose: 5 mg. Total Dexamethasone equivalent dose: 20 mg. In the UK, intensive care unit patients frequently receive steroids for many other reasons, and it may not be possible or ethical to perform a prospective placebo-controlled trial to clearly address the laryngeal oedema question. Most admissions are post-operative or for sepsis support. Surgical patients may already have received 8-10 mg of intra-operative dexamethasone, which is commonly used with other anti-emetics to prevent post-operative nausea and vomiting.[2] This may still be active at 3-5 days. Patients with poorly responsive septic shock, in accordance with updated international guidelines,[3] may be receiving hydrocortisone 200- 300 mg daily in divided doses (7.5-11.25 mg dexamethasone). References [1] Fan T, Wang G, Mao B, Xiong Z, Zhang Y, Liu X, Wang L, Yang S. Prophylactic administration of parenteral steroids for preventing airway complications after extubation in adults: meta-analysis of randomised placebo controlled trials. BMJ 2008;337:a1841. [2] Henzi I, Walder B, Tramèr MR. Anesth Analg. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. 2000;90(1):186-94. [3] Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296-327. Competing interests: None declared |
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Joseph L Mathew, Assistant Professor (Pediatric Pulmonology) Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160012
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A Cochrane review published on this subject in 2008(1) that included an exhaustive literature search till April 2007 concluded that overall, parenteral steroid prophylaxis has no beneficial effect on the need for reintubation or development of stridor in the pediatric age group (newborns, infants and older children). Interestingly, this review contradicted a previous version that showed beneficial effect on stridor in the neonatal age group(2). Post-hoc sub-group analysis of the updated review suggested that multiple doses and administration more than six hours prior to extubation reduced the risk of stridor, although there was no beneficial effect on reintubation. The beneficial effect in neonates appeared to be substantiated by a Cochrane review (3), that is unfortunately out of date at present. As the issue is a very important one, I conducted an additional updated search beyond April 2007 using a broad (sensitive) search strategy with the terms ‘steroid extubation’ and ‘steroid intubation’. This search on 18 April 2008 yielded 15 and 97 citations respectively. One additional relevant publication for the pediatric age group was identified, but could not be accessed since it was in Chinese(4). The Cochrane review as well as the recent meta-analysis (5) both suggest that parenteral steroids have a prophylactic role in adult patients. Since there is no evidence of efficacy in the pediatric age group, pediatricians are left to make their own choices. However, it should be noted that "absence of evidence of efficacy" is not synonymous with "evidence of absence of efficacy". Using these arguments, I noted earlier this year(6)that going strictly by the principles of evidence based medicine, there is nothing to warrant a change from existing practice in individual pediatric and neonatal intensive care units. However it may be possible that multiple doses of steroids, administered at least 12 hours prior to extubation is beneficial in children as well. The answer can only be provided through an appropriate randomised controlled trial. References 1. Markovitz BP, Randolph AG, Khemani RG. Corticosteroids for the prevention and treatment of postextubation stridor in neonates, children and adults. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD001000. DOI: 10.1002/14651858.CD001000.pub2. 2. Markovitz BP, Randolph AG. Corticosteroids for the prevention and treatment of post-extubation stridor in neonates, children and adults. Cochrane Database Syst Rev. 2000;(2):CD001000. 3. Davis PG, Henderson-Smart DJ. Intravenous dexamethasone for extubation of newborn infants. Cochrane Database Syst Rev. 2001;(4):CD000308. 4. Chen ZL. Can dexamethasone be recommended for routine use for extubation and mechanical ventilation withdrawal in very low birth weight infants. Zhongguo Dang Dai Er Ke Za Zhi. 2007; 9: 260-3. 5. Fan T, Wang G, Mao B, Xiong Z, Zhang Y, Liu X, wang L, Yang S. Prophylactic administration of parenteral steroids for preventing airway complications after extubation in adults: meta-analysis of randomised placebo controlled trials. BMJ 2008; 337: a1841 6. Mathew JL. Role of Parenteral Steroids to Prevent Extubation Failure in Ventilated Children. Indian Pediatr 2008; 45: 483-486. Competing interests: None declared |
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Fernando Martins do Vale, Professor of Pharmacology Instituto de Farmacologia e Neurociências - Faculdade Medicina Lisboa
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Sir. Despite the use of tracheal tubes with low-pressure cuff, postextubation laryngeal oedema is a frequent and severe complication of tracheal intubation that typically occurs shortly after extubation . The meta-analysis of Fan et al.(2008) concluded that the prophylactic administration of parenteral steroids in multidose regimens before planned extubation reduces the incidence of laryngeal oedema after extubation and the consequent reintubation rate in adults. The study does not consider the timing of doses before extubation, although they refer better results with multidose treatments (mean steroid dose equivalent to 160 mg methylprednisolone), which implicitly requires several hours of treatment. They also concluded that further trials are needed to establish the optimal dose of steroids and the optimal time between the start of treatment and planned extubation. This late statement deserves some comments. Indeed the majority of antiinflammatory effects of corticosteroids result from interferences with the expression of genes responsible for the synthesis of immunologic/inflammatory mediators or for the cellular migration and activity. So, for the emergence of the anti-inflammatory effect it is necessary a latency period of several hours. The delay needed to modify gene expression and produce useful antiinflammatory effects, is well illustrated by the study of Francois et al.(2007)included in Fan meta-analysis, showing that on ventilated patients the administration of only 80mg methylprednisolone, was highly effective in reducing the incidence of postextubation laryngeal oedema when given 12h before planned extubation. This latter study illustrates the importance of knowing the mechanism of action of corticosteroids, which explains their late effects and may be critical to optimize therapeutic outcomes. Fernando Martins do Vale, PhD, MD. Competing interests: None declared |
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Cecily M D Don, SpR Anaesthesia Borders General Hospital, Melrose TD6 9BS., Jonathan P Aldridge, Consultant, Anaesthesia & Intensive Care Medicine, Borders General Hospital, Melrose TD6 9BS.
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The meta-analysis carried out by Fan et al highlights the importance of careful planning of extubation in Intensive Care.[1] In our institution it is routine practice to use endotracheal tubes with high-volume low pressure cuffs, and to confirm leak around the deflated cuff before extubation. In the past 10 years in our unit we have cared for 1081 patients who had >24 hours endotracheal intubation. We are unable to identify a case where reintubation was required for unanticipated airway oedema alone (Major laryngeal oedema as defined by Fan et al[1]). We have identified one case of post extubation stridor (Minor laryngeal oedema [1]). We believe that the true indicence of clinically relevant post extubation laryngeal oedema is in fact much lower than that quoted in the meta-analysis. This would mean the number needed to treat would be considerably higher than quoted. The meta-analysis included papers written in the last 30 years, over which time equipment and practice has changed considerably. We feel that the risks associated with steroid use and of delaying extubation until steroids take effect to prevent such a rare complication are outweighed by the benefits of careful planned extubation. Future work should therefore be directed at identifying the current incidence of post extubation airway oedema and its complications. Only then should we consider investigating further the use of routine prophylactic steroid treatment prior to extubation in modern adult Intensive Care. Cecily M D Don, Spr Anaesthesia. cecdon@doctors.org.uk Jonathan P Aldridge, Consultant, Anaesthesia & Intensive Care Medicine Borders General Hospital, Melrose TD6 9BS. 1. Tao Fan, Gang Wang, Bing Mao, et al. Prophylactic administration of parenteral steroids for preventing airway complications after extubation in adults: meta-analysis of randomised placebo controlled trials. BMJ 2008;337:a1841 Competing interests: None declared |
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Mohamad Said Maani Takrouri, Consultant King Fahad Medical City Riyadh Saudi Arabia, Omer Talab, Consultant Ahsan Zafrullah Consultant Sabry Radwan Assistant Consultant
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I read with interest the systemic review and meta-analysis carried out by Fan T, et al. It highlights the dilemma of of extubation in Intensive Care, and indicated the uncertainty regarding its benefit and the value of this study to settle this issue.[1]
it was rather confusing at the end, whether we can extrapolate the results toward specific bad outcome prophylaxis against laryngeal edema (LE) and risk of severe LE necessitating re-intubation, in other settings, like long surgery on intubated patients - or not. There were no references to the indication of intubation in the studies included the paper, neither references to co morbidities, or the quality regimen of tube care, tube type and cuff quality, length of insertion, cuff pressure and frequency of replacement. In the absence of technical factors unifications we could not take the recommendations of this paper for granted. Tube factor, length of insertion, the degree of sedation, the presence of coughing on the tube and co morbidities are very valid factors to induce LE
Traumatic or rough handling of endotracheal tube could be relevant in producing LE even after short period of insertion. There is no specific steroid regimen which should be followed whether Dexamethasone or Methyl Predinsolone with different pharmacokinetics as the dose and timing to give the dose or doses before extubation,though it was mentioned in the paper that it need to be studied further. It should be addressed in such type of study. It should emphasize that the incidence of LE from this study is variable and reflect unknown factor related to variability of the trials studied. The reasons for intubation may be variable and it is very much difficult to restrict it to only severe LE.
1. Tao Fan, Gang Wang, Bing Mao, et al. Prophylactic administration of parenteral steroids for preventing airway complications after extubation in adults: meta-analysis of randomised placebo controlled trials. BMJ 2008;337:a1841
Competing interests: None declared |
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Mohamad Said Maani Takrouri, Consultant King Fahad Medical City Riyadh Saudi Arabia, Omer Talab, Consultant Ahsan Zafrullah Consultant . Sabry Radwan Assistant Consultant
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I read with interest the systemic review and meta-analysis carried out by Fan T, et al. It highlights the dilemma of of extubation in Intensive Care, and indicated the uncertainty regarding its benefit and the value of this study to settle this issue.[1]
It was rather confusing at the end, whether we can extrapolate the results toward specific bad outcome prophylaxis against laryngeal edema (LE) and risk of severe LE necessitating re-intubation, in other settings, like long surgery on intubated patients - or not. There were no references to the indication of intubation in the studies included the paper, neither references to co morbidities, or the quality regimen of tube care, tube type and cuff quality, length of insertion, cuff pressure and frequency of replacement. In the absence of technical factors unifications we could not take the recommendations of this paper for granted. Tube factor, length of insertion, the degree of sedation, the presence of coughing on the tube and co morbidities are very valid factors to induce LE Traumatic or rough handling of endotracheal tube could be relevant in producing LE even after short period of insertion. There is no specific steroid regimen which should be followed whether Dexamethasone or Methyl Predinsolone with different pharmacokinetics as the dose and timing to give the dose or doses before extubation,though it was mentioned in the paper that it need to be studied further. It should be addressed in such type of study. It should emphasize that the incidence of LE from this study is variable and reflect unknown factor related to variability of the trials studied. The reasons for intubation may be variable and it is very much difficult to restrict it to only severe LE. 1. Tao Fan, Gang Wang, Bing Mao, et al. Prophylactic administration of parenteral steroids for preventing airway complications after extubation in adults: meta-analysis of randomised placebo controlled trials. BMJ 2008;337:a1841 Competing interests: None declared |
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Tony K Chow, Staff Anaesthestist Department of Anaesthesia & Peri-Operative Medicine, Box Hill Hospital, Box Hill, Victoria, Australia 3128
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To the Editor: Let me congratulate Fan et al. for their comprehensive systematic review regarding the prophylactic use of steroids in preventing extubation oedema.1 Congratulations must also be extended to the Cochrane Collaboration and to the authors who conducted the randomised controlled trials (RCTs) referenced within the review. It is exactly 30 years since Archie Cochrane uttered the following words that sparked the “Evidence Based Medicine” movement: “It is surely a great criticism of our profession that we have not organised a critical summary, by specialty or subspecialty, adapted periodically, of all randomised controlled trials.”2 Despite the efforts by Fan et al. however, clearly we have yet to fulfill Cochrane’s challenge. In particular, we are bogged down by methods used to identify the quality RCTs that enable periodic updating of the reviews. As stated in Figure 1 by Fan et al., 1500 citations were screened in order to identify the six eligible RCTs for review. The current method1 is time consuming and expensive, and it is difficult, if not impossible, to duplicate the search to validate the original authors’ results. I would like to suggest a simpler solution: (double blind$ or random$).af. This single-line algorithm applied to MEDLINE and EMBASE identifies a sufficient number of RCTs (greater than 95%) compared with the number identified in the original reviews, in order to draw the same conclusions.3 In comparison to Fan et al., the search strategy as described in Table 1 creates a readily reproducible database of 43 citations that identified all six RCTs that were included in review. There were in fact only 39 citations to evaluate in detail due to minor differences in the way the articles were referenced that was not excluded by computer. This highlights the high specificity of this search strategy: the strategy has demonstrated 98% specificity (i.e. every 100 articles identified two were non-RCTs)3 in pain relief research in its original publication. I invite the Fan et al. and other reviewers interested in this area to test our strategy in an effort to expedite the fulfillment of the Cochrane Challenge. Tony K. F. Chow MBBS, BMedSci, FANZCA
Table 1 Searches Results 1. (double blind$ or random$).af. 1038021 2. extubat$.af. 12609 3. (oedema or edema).af. 2022246 4. 1 and 2 and 3. 72 5. Remove duplicates from 4. 52 6. limit 5 to humans. 43 Search conducted on the 21st of January 2009, applied to EMBASE 1980 to 2009 week 03 and Ovid MEDLINE(R) 1950 to January Week 1 2009. References 1. Fan T, Wang G, Mao B, Xiong Z, Zhang Y, Liu X Wang L, Yang S. Prophylactic administration of parenteral steroids for preventing airway complications after extubation in adults: meta-analysis of randomised placebo controlled trials. BMJ 2008;337:a1841 doi:10.1136/bmj.a1841 2. Cochrane AL. 1931-1971: a critical review, with particular reference to the medical profession. In: Medicines for the year 2000. London: Office of Health Economics 1979:1-11 3. Chow TKF, To E, Goodchild CS, McNeil JJ. A simple, fast, easy method to identify the evidence base in pain-relief research: validation of a computer search strategy used alone to identify quality randomized controlled trials. Anesth Analg 2004:98:1557-65 Competing interests: None declared |
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