- Email: [email protected]
Selenium supplementation for critical illness
Correspondence
We declare that we have no conflicts of interest.
Alejandro Forner, *Jordi Bruix [email protected] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain (AF, JB); and BCLC Group, Liver Unit, Hospital Clínic, 08036 Barcelona, Spain (AF, JB) 1
Poustchi H, Farrell GC, Strasser SI, Lee AU, McCaughan GW, George J. Feasibility of conducting a randomized control trial for liver cancer screening: is a randomized controlled trial for liver cancer screening feasible or still needed? Hepatology 2011; 54: 1998–2004.
www.thelancet.com Vol 380 August 4, 2012
2
3 4
5
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020–22. EASL-EORTC. Management of hepatocellular carcinoma. J Hepatol 2012; 56: 908–43. Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011; 3: CD004787. Forner A, Llovet JM, Bruix J. Chemoembolization for intermediate HCC: is there proof of survival benefit? J Hepatol 2012; 56: 984–86.
trial on which this statement is based was done only in sheep.5 Studies on human beings are needed. Thus, although selenium concentrations in the plasma of critically ill patients are lower than normal, whether selenium supplementation is effective warrants further study. We declare that we have no conflicts of interest.
Zhengdong Kong, *Zhaofan Xia
Selenium supplementation for critical illness
[email protected]
In her Review on selenium and health (March 31, p 1256),1 Margaret Rayman discusses the relation between critical illness and selenium. There might be some small flaws that deserve further discussion. Rayman mentions two metaanalyses, which she states show a trend towards decreased mortality in critically ill patients after selenium supplementation. We have doubts about that conclusion. One of the studies2—a systematic review including 436 patients—did conclude that mortality in critically ill patients was decreased significantly after selenium supplementation. But this review lacked inclusion and exclusion criteria, and was dominated by a single trial,3 which could affect the reliability of the results. The other study4—a meta-analysis with 1172 patients—was more persuasive, but concluded that selenium supplementation did not significantly decrease mortality in critically ill patients. Besides, a meta-analysis that we are doing shows that selenium supplementation does not affect mortality in patients with sepsis (n=530, relative risk 0·89, 95% CI 0·73–1·07, p=0·21). Therefore, we judge that there is insufficient evidence to show that selenium supplementation can benefit either critically ill patients or patients with sepsis. Additionally, Rayman mentions that a large-bolus injection is more effective than continuous administration. But it is a pity that the
2
Department of Burn Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China 1
3
4
5
Rayman MP. Selenium and human health. Lancet 2012; 379: 1256–68. Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med 2005; 31: 327–37. Angstwurm MW, Engelmann L, Zimmermann T, et al. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med 2007; 35: 118–26. Avenell A, Noble DW, Barr J, Engelhardt T. Selenium supplementation for critically ill adults. Cochrane Database Syst Rev 2004; 4: CD003703. Wang Z, Forceville X, Van Antwerpen P, et al. A large-bolus injection, but not continuous infusion of sodium selenite improves outcome in peritonitis. Shock 2009; 32: 140–46.
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than in other parts of the world and can induce cirrhosis. This diagnosis underlies hepatocellular carcinoma in 25 of 26 patients in the two studies they quote. In the absence of cohort studies to define the incidence of hepatocellular carcinoma in MOVC, the screening recommendation could not exceed the general one for cirrhosis of any cause. We noted that radioembolisation had antitumoral activity, but that controlled trials were needed to prove a survival benefit. Maurice van den Bosch and Luc Defreyne claim that they are running such a trial. Unfortunately, they use time to progression, instead of survival, as the primary endpoint. Finally, Roberto Oliveri and colleagues question the robustness of the evidence to support transarterial (chemo) embolisation (TAE/TACE) and quote their meta-analysis.4 As mentioned in our Seminar, the inclusion of studies that do not deal with the survival effect of TACE in the proper target population impairs the information. At the same time, retaining studies that used gelfoam powder, which is known to be deleterious, further raises the risk of confusion. If this is not taken into account and other trials are excluded according to Oliveri and colleagues’ definition of bias, the final meta-analysis is not robust. These limitations have been noted in the recent guidelines from the European Association for the Study of the Liver and the European Organisation for Research and Treatment of Cancer.2,5 Expert knowledge is key to assessing the quality of the data used for meta-analysis.
Author’s reply Zhengdong Kong and Zhaofan Xia express doubt as to whether I correctly described the outcome of studies of selenium supplementation in critical illness. I stated that two metaanalyses showed that mortality tended to decrease when patients with systemic inflammatory response syndrome or septic shock were treated with selenium. This is indeed the case: the first meta-analysis1 showed that, across seven studies (n=186), selenium supplementation (alone and in combination with other antioxidants) was associated with a trend towards lower mortality (relative risk 0·59, 95% CI 0·32–1·08; p=0·09), and the second2 showed a similar trend towards reduced overall mortality (risk ratio 0·75, 95% CI 0·53–1·06) which became significant 471
We declare that we have no conflicts of interest.
Alejandro Forner, *Jordi Bruix [email protected] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain (AF, JB); and BCLC Group, Liver Unit, Hospital Clínic, 08036 Barcelona, Spain (AF, JB) 1
Poustchi H, Farrell GC, Strasser SI, Lee AU, McCaughan GW, George J. Feasibility of conducting a randomized control trial for liver cancer screening: is a randomized controlled trial for liver cancer screening feasible or still needed? Hepatology 2011; 54: 1998–2004.
www.thelancet.com Vol 380 August 4, 2012
2
3 4
5
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020–22. EASL-EORTC. Management of hepatocellular carcinoma. J Hepatol 2012; 56: 908–43. Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011; 3: CD004787. Forner A, Llovet JM, Bruix J. Chemoembolization for intermediate HCC: is there proof of survival benefit? J Hepatol 2012; 56: 984–86.
trial on which this statement is based was done only in sheep.5 Studies on human beings are needed. Thus, although selenium concentrations in the plasma of critically ill patients are lower than normal, whether selenium supplementation is effective warrants further study. We declare that we have no conflicts of interest.
Zhengdong Kong, *Zhaofan Xia
Selenium supplementation for critical illness
[email protected]
In her Review on selenium and health (March 31, p 1256),1 Margaret Rayman discusses the relation between critical illness and selenium. There might be some small flaws that deserve further discussion. Rayman mentions two metaanalyses, which she states show a trend towards decreased mortality in critically ill patients after selenium supplementation. We have doubts about that conclusion. One of the studies2—a systematic review including 436 patients—did conclude that mortality in critically ill patients was decreased significantly after selenium supplementation. But this review lacked inclusion and exclusion criteria, and was dominated by a single trial,3 which could affect the reliability of the results. The other study4—a meta-analysis with 1172 patients—was more persuasive, but concluded that selenium supplementation did not significantly decrease mortality in critically ill patients. Besides, a meta-analysis that we are doing shows that selenium supplementation does not affect mortality in patients with sepsis (n=530, relative risk 0·89, 95% CI 0·73–1·07, p=0·21). Therefore, we judge that there is insufficient evidence to show that selenium supplementation can benefit either critically ill patients or patients with sepsis. Additionally, Rayman mentions that a large-bolus injection is more effective than continuous administration. But it is a pity that the
2
Department of Burn Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China 1
3
4
5
Rayman MP. Selenium and human health. Lancet 2012; 379: 1256–68. Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med 2005; 31: 327–37. Angstwurm MW, Engelmann L, Zimmermann T, et al. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med 2007; 35: 118–26. Avenell A, Noble DW, Barr J, Engelhardt T. Selenium supplementation for critically ill adults. Cochrane Database Syst Rev 2004; 4: CD003703. Wang Z, Forceville X, Van Antwerpen P, et al. A large-bolus injection, but not continuous infusion of sodium selenite improves outcome in peritonitis. Shock 2009; 32: 140–46.
Science Photo Library
than in other parts of the world and can induce cirrhosis. This diagnosis underlies hepatocellular carcinoma in 25 of 26 patients in the two studies they quote. In the absence of cohort studies to define the incidence of hepatocellular carcinoma in MOVC, the screening recommendation could not exceed the general one for cirrhosis of any cause. We noted that radioembolisation had antitumoral activity, but that controlled trials were needed to prove a survival benefit. Maurice van den Bosch and Luc Defreyne claim that they are running such a trial. Unfortunately, they use time to progression, instead of survival, as the primary endpoint. Finally, Roberto Oliveri and colleagues question the robustness of the evidence to support transarterial (chemo) embolisation (TAE/TACE) and quote their meta-analysis.4 As mentioned in our Seminar, the inclusion of studies that do not deal with the survival effect of TACE in the proper target population impairs the information. At the same time, retaining studies that used gelfoam powder, which is known to be deleterious, further raises the risk of confusion. If this is not taken into account and other trials are excluded according to Oliveri and colleagues’ definition of bias, the final meta-analysis is not robust. These limitations have been noted in the recent guidelines from the European Association for the Study of the Liver and the European Organisation for Research and Treatment of Cancer.2,5 Expert knowledge is key to assessing the quality of the data used for meta-analysis.
Author’s reply Zhengdong Kong and Zhaofan Xia express doubt as to whether I correctly described the outcome of studies of selenium supplementation in critical illness. I stated that two metaanalyses showed that mortality tended to decrease when patients with systemic inflammatory response syndrome or septic shock were treated with selenium. This is indeed the case: the first meta-analysis1 showed that, across seven studies (n=186), selenium supplementation (alone and in combination with other antioxidants) was associated with a trend towards lower mortality (relative risk 0·59, 95% CI 0·32–1·08; p=0·09), and the second2 showed a similar trend towards reduced overall mortality (risk ratio 0·75, 95% CI 0·53–1·06) which became significant 471