Correspondence

lyme, Q-fever, listeriosis, yellow fever, varicella, influenza, etc) should warrant early clamping. It would be easy to check this assertion for Rhesus antigens. If more antigens migrate during those 2 extra mins, against the pressure gradient, then increased migration of much smaller microorganisms with the pressure gradient seems likely. I declare no competing interests.

Douwe Arie Verkuyl [email protected]

I declare no competing interests.

Refaja Hospital,Stadskanaal, 9500AC Netherlands.

Daniele Focosi

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[email protected]

Vain NE, Satragno DS, Gorenstein AN, et al. Effect of gravity on volume of placental transfusion: a multicentre, randomised, non-inferiority trial. Lancet 2014; 384: 235–40.

The findings by Nestor Vain and colleagues1 confirm the straightforwardness of the universal use of delayed cord blood clamping as routine obstetric practice. As the Article points out, this practice goes against umbilical cord blood donation.2 In a phase of worldwide exponential increase, the Bone Marrow Donor Wordwide registry reports, as of Oct 8, 2014, 616 997 banked cord blood units and about 30 000 cord blood transplants performed. Because about 90% of collections contain less than 1·5 million nucleated cells (a commonly used threshold for banking), more than 5 million newborns have been denied their cord blood without any social benefit, after the cost incurred by parents for pre-delivery examinations and the potential harm to the health of newborns.3 From the primum non nocere point of view, cord blood collection seems unethical. However, nowadays, cord blood is presented as clinical waste, a by-product of birthing, and a gift made available to a global exchange-based bioeconomy;4 moreover, emotional advertising campaigns have facilitated the growth of private profit-making cord blood banks aimed at autologous use. The trend to retarget unbankable cord blood units to blood derivatives (mainly plasma eye drops or platelet 1668

gel) or cell therapy products is of little use since alternative and more cost-effective sources exist from voluntary adult blood donations.5 Adding to this scenario, the need for multiple cord blood units per adult recipient, the high rate of engraftment failure, and the increased cost of admission to hospital due to delayed engraftment, I conclude that the cost-to-benefit ratio of the whole procedure undermines its sustainability.

University of Pisa, Department of Translational Research, Via Roma 56, Pisa, PI 56100, Italy 1

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Vain NE, Satragno DS, Gorenstein AN, et al. Effect of gravity on volume of placental transfusion: a multicentre, randomised, non-inferiority trial. Lancet 2014; 384: 235–40. Raju T. Delayed cord clamping: does gravity matter? Lancet 2014; 384: 213–14. McDonald SJ, Middleton P, Dowswell T, Morris PS. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcome. The Cochrase Databaic Syws Rev 2013; 7: Cd004074. Brown N. Contradictions of value: between use and exchange in cord blood bioeconomy. Sociol Health Illn 2013; 5: 97–11. Parazzi V, Lazzari L, Rebulla P. Platelet gel from cord blood: a novel tool for tissue engineering. Platelets 2010; 21: 549–54.

Authors’ reply We thank Christiane Schwarz, Douwe Arie Verkuyl, and Daniele Focosi for their interest in our study.1 Schwarz brings up several aspects that deserve consideration. The only hospital in which mothers received epidural anaesthesia included 129 infants. It is correct that most of the mothers received oxytocin during labour, but the doses, timing, and duration of infusion were variable because, ours being a pragmatic study, the administration of oxytocin was decided by each obstetrician. Since all the mothers in the study delivered in beds, we have no way of answering the question related to the influence of the vertical position on the amount of placental transfusion, and the same answer applies to caesarean section deliveries. Trials can only address

the effect of the outcome variable specifically on the studied population. The percentage of deliveries with operative procedures is representative of the practice at the participating hospitals, and although the risks may be different to those in developed countries, it seems quite unlikely that gravity would influence the volume of placental transfusion in an even lower risk population. Schwarz’s judgment that 3·6% of newborns in need of resuscitation in our study is “very high” does not seem adequate; the American Academy of Pediatrics reports that about 10% of infants need some assistance to begin breathing at birth.2 Furthermore, in our trial, intended to assess only healthy newborns, any sign that could suggest that an infant might need resuscitation was sufficient reason for its exclusion from the study. We appreciate Verkuyl’s concerns about the applicability of delayed cord clamping in several specific circumstances. Although possible, an increase in the risks of any of the infections mentioned by Verkuyl by the extra blood transferred with delayed cord clamping has never been demonstrated. Although it is frequently recommended to clamp the cord immediately after birth in Rhesus incompatibility, the practice is not based on well designed clinical trials. The suggestion that early clamping of the cord could prevent transmission of certain infectious agents to the infant is at the present time merely speculative. However, it has been clearly shown that delayed cord clamping decreases iron deficiency in infancy,3,4 a highly prevalent serious problem worldwide, especially in the areas where the infections mentioned by Verkuyl are particularly frequent. We entirely agree with Focosi’s thoughtful comments about the, at least, debatable usefulness of cord blood banking for future transplants and on the use for other less conventional purposes. Perhaps, an exception could be specific diseases www.thelancet.com Vol 384 November 8, 2014

Correspondence

We declare no competing interests.

*Nestor E Vain, Luis M Prudent, Daniela S Satragno, Juan E Gordillo, Adriana N Gorenstein [email protected] Foundation for Maternal and Child Health (FUNDASAMIN), Honduras 4160, Buenos Aires, Argentina (NEV, LMP, DSS, AN); and Institute of Maternity Our Lady of Mercy, San Miguel de Tucumán, Argentina (JEG) 1

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Vain NE, Satragno DS, Gorenstein AN, et al. Effect of gravity on volume of placental transfusion: a multicentre, randomised, non-inferiority trial. Lancet 2014; 384: 235–40. Kattwinkel J, Perlman JM, Aziz K, et al. Neonatal resuscitation: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics 2010; 126: e1400–13. Chaparro CM, Neufeld LM, Tena Alavez G, Eguia-Líz Cedillo R, Dewey KG. Effect of timing of umbilical cord clamping on iron status in Mexican infants: a randomized controlled trial. Lancet 2006; 367: 1997–2004. Ceriani Cernadas JM, Carroli G, Pellegrini L, et al. The effect of early and delayed umbilical cord clamping on ferritin levels in term infants at six months of life: a randomized, controlled trial. Arch Argent Pediatr 2010; 108: 201–08 (in Spanish). Bewley S, Díaz-Rossello JL, Mercer J. Natural stem cell transplantation: interventions, nuances and ethics. J Cell Mol Med 2010; 14: 2840–41.

Positive end-expiratory pressure during surgery With great interest, I read the Article by PROVE Network Investigators (Aug 9, p 495)1 and the accompanying Comment. 2 Some of the study limitations that might have obscured any treatment effect (eg, protocol deviations, infrequent recruitment manoeuvres, and a high positive end-expiratory pressure [PEEP] level in the higher PEEP group) have been addressed in the accompanying Comment.2 Several additional factors might have negated any potential treatment effect. www.thelancet.com Vol 384 November 8, 2014

39% of patients in both groups had received thoracic epidural analgesia. Compared with systemic analgesia, thoracic epidural analgesia can be expected to improve the postoperative pulmonary outcome in patients undergoing abdominal surgery.3 At the same time, the combination of thoracic epidural analgesia, general anesthesia, and mechanical ventilation frequently causes hypotension, which requires therapy.4 Any possible difference in pulmonary outcome between groups might have been obscured by the beneficial pulmonary effects of thoracic epidural analgesia. Similarly, the higher incidence of intraoperative hypotension and increased need for vasoactive drugs in the high compared with the low PEEP group might not have mainly been caused by the high PEEP per se but instead by the combination of high PEEP, thoracic epidural analgesia, and general anaesthesia. To compare the primary and secondary outcome variables between patients with and without thoracic epidural analgesia would be relevant. Combined abrupt withdrawal of 12 cm H2O PEEP and restoration of spontaneous respiration at the time of extubation will have acutely increased venous return and, in turn, right and left ventricular preload. This might have increased lung water in patients with left ventricular dysfunction with unpredictable subsequent adverse pulmonary sequelae. All patients had received intermediate longacting muscle relaxants. Residual neuromuscular blockade must be expected at the end of surgery in up to 80% of cases.5 Residual neuromuscular blockade is associated with impaired postoperative lung function and postoperative pulmonary morbidity.5,6 Because the detrimental effect of residual neuromuscular blockade on postoperative pulmonary outcome might have obscured any potential treatment effects, we need to know whether neuromuscular function was quantitatively assessed before extubation.

Extubation during an inspired oxygen fraction (FiO 2) of 1·0 is associated with worse post-extubation atelectasis and oxygenation compared with extubation at a lower FiO2.7 Use of an FiO2 of 1·0 at the time of extubation in all patients might partly explain the absence of difference in postoperative atelectasis. I declare no competing interests.

Hans-Joachim Priebe [email protected] Department of Anaesthesia, University Hospital Freiburg, Freiburg im Breisgau 79106, Germany 1

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The PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet 2014; 384: 495–503. Futier E. Positive end-expiratory pressure in surgery: good or bad? Lancet 2014; 384: 472–74. Pöpping DM, Elia N, Marret E, Remy C, Tramèr MR. Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery. A meta-analysis. Arch Surg 2008; 143: 990–99. De Kock M, Laterre P-F, Andruetto P, et al. Ornipressin (Por 8): an efficient alternative to counteract hypotension during combined general/epidural anesthesia. Anesth Analg 2000; 90: 1301–07. Plaud B, Debaene B, Donati F, Marty J. Residual paralysis after emergence from anesthesia. Anesthesiology 2010; 112: 1013–22. Berg H, Viby-Mogensen J, Roed J, et al. Residual neuromuscular block is a risk factor for postoperative pulmonary complications: A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand 1997; 41: 1095–103. Benoît Z, Wicky S, Fischer J-F, et al. The effect of increased FiO2 before tracheal extubation on postoperative atelectasis. Anesth Analg 2002; 95: 1777–81.

We read with interest the PROVHILO study 1 comparing high with low positive end-expiratory pressure (PEEP) during general anaesthesia for open abdominal surgery. The researchers concluded that high PEEP and recruitment manoeuvres during open abdominal surgery do not protect against postoperative pulmonary complications. 1 We commend the investigators for providing such highly needed data; however, we believe that a major contributing factor that could

Jim Varney/Science Photo Library

amenable to treatment with stem cells when a sibling is born. Bewley and colleagues 5 describe our thinking quite well: “There is no proven benefit of interrupting umbilical blood flow before its natural cessation. Until then, the only ethical bank recipient is the newborn infant.”

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