BJA
Correspondence
weighing more than 100–150 kg. While surface landmarks may identify proper needle entry point, the tip may vary greatly as it traverses longer distances, as in the case of obesity. We would like to encourage the authors to use a technique that minimizes repositioning while maintaining the patient in a supine position, namely ilioinguinal/iliohypogastric nerve block. This type of block is ideal for the obese and muscular patients that may be augmented with mild to moderate sedation.
Declaration of interest None declared. C. Z. Kakazu* M. Lippmann California, USA * E-mail: [email protected]
doi:10.1093/bja/aeu028
Cardiac arrest after liver transplantation in a patient with takotsubo cardiomyopathy Editor—We report a patient, 52-yr-old male, with normal pretransplant cardiac workup who underwent orthotopic liver transplantation for end-stage liver disease due to haemochromatosis and alcohol use. The procedure was uncomplicated with a normal transoesophageal echocardiogram; however, the patient developed pulseless ventricular tachycardia after surgical closure. Cardiopulmonary resuscitation was performed with return of spontaneous circulation within 60 s. He was transferred to the intensive care unit (ICU) on amiodarone, norepinephrine, and vasopressin infusions. He was in sinus tachycardia 100–117 beats min21, with central venous pressure 14–16 cm H2O, pulmonary artery systolic pressure 38–42 cm H2O, and cardiac output 7–10 litre min21. Initial troponin level was 0.22 ng ml21 and electrocardiogram showed new anteroseptal Q waves with minimal ST elevation and lateral T wave inversions. Immediate bedside transthoracic echocardiogram exhibited mid-to-distal and apical akinesia. Basal segments exhibited preserved wall function, but overall ejection fraction remained 25%. Left heart catheterization was performed, which showed no arterial stenosis or occlusions. Takotsubo cardiomyopathy was diagnosed and vasopressors were changed to milrinone and phenylephrine. Troponin level peaked at 7.48 ng ml21 on postoperative day 1. The patient was extubated and weaned off milrinone and phenylephrine on postoperative day 5. Echocardiogram was unchanged on postoperative day 6 but showed normal cardiac function when repeated on postoperative day 18 (Fig. 1A – D). Meanwhile, liver function tests continually improved from the day of surgery, and the transaminases were normal by postoperative day 9.
594
Takotsubo cardiomyopathy, also known as transient apical ballooning syndrome, stress-induced cardiomyopathy, or ‘broken heart syndrome,’ gets its name from the Japanese word for ‘fishing pot for trapping octopus’, based on the pathological appearance of the left ventricle.1 It was first described in Japan over 20 yr ago and since then has been described in a variety of clinical scenarios. The most common pathological finding is focal myocytolysis. The cardiomyopathy is distinctive because the apical wall of the left ventricle is affected, but the base is spared. Some have proposed that the apex is more vulnerable due to its limited elasticity reserve from not having a three layered myocardial configuration.2 Moreover, the apex has a limited coronary circulation and its increased b-receptor density makes it more sensitive to adenylate stimulation. The most common characteristics are: predominant occurrence in elderly or post-menopausal women; ST elevation/depression or T wave changes; onset after an acute emotional stress or an acute medical condition; prolonged QT interval; akinesis of the apical and distal anterior wall and hypercontraction of the basal wall; mild increase in cardiac enzymes; complete resolution of apical wall motions abnormality and the depressed left ventricular systolic function.1 Cases of takotsubo cardiomyopathy have been reported in the setting of liver transplantation,3 but this is the first description presenting as cardiac arrest immediately after transplantation. Awareness of the condition and early echocardiographic
Downloaded from http://bja.oxfordjournals.org/ by guest on April 11, 2015
1 Mokini Z, Buccino G, Vitale G, Mauri T, Fumagalli R, Pesnti A. Psoas compartment block for anaesthesia during surgical repair of inguinal hernias. Br J Anaesth 2013; 111: 298– 9
Fig 1 (A) The left ventricle with mitral valves open, in mid-diastole. (B) The left ventricle in end systole, with mitral valves closed. (A) and (B) were obtained 20 min after cardiac arrest. (B) demonstrates apical ballooning, with preserved proximal contractility. (C) and (D) were obtained 17 days later. (C) The left ventricle with the mitral valves open, in mid-diastole. (D) The left ventricle with mitral valves closed, in end systole. There is now normal apical contractility and normal systolic function.
BJA
Correspondence
evaluation are imperative for making this diagnosis. The condition can have a good prognosis if diagnosed early and aggressive supportive management is initiated. The expanding use of point-of-care ultrasound in the ICU will likely lead to increased recognition of this condition.
Declaration of interest None declared.
Funding D.J.W. receives research support from the NIH (NHLBI-K12HL109068).
1 Wittstein IS, Thiemann DR, Lima JAC, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352: 539– 48 2 Mori HH, Ishikawa SS, Kojima SS, et al. Increased responsiveness of left ventricular apical myocardium to adrenergic stimuli. Cardiovasc Res 1993; 27: 192– 8 3 Tachotti Pires LJ, Cardoso Curiati MN, Vissoci Reiche F, et al. Stress-induced cardiomyopathy (takotsubo cardiomyopathy) after liver transplantation-report of two cases. Transplant Proc 2012; 44: 2497– 500
doi:10.1093/bja/aeu029
Open letter to the Executive Director of the European Medicines Agency concerning the licensing of hydroxyethyl starch solutions for fluid resuscitation Editor—We have sent this letter to the Executive Director of the European Medicines Agency: we are concerned that the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee’s (PRAC) recent conclusions on the use of hydroxyethyl starch (HES)1 will result in harm to patients. In June, the PRAC recommended the suspension of marketing authorization for HES, as the available evidence demonstrated that any possible benefits from HES no longer outweigh its risk.2 On October 11, 2013, the PRAC revised its conclusions, announcing that ‘HES must no longer be used to treat patients with sepsis or burns injuries or in critically ill patients because of an increased risk of kidney injury and mortality. HES solutions may, however, continue to be used in patients to treat hypovolaemia caused by acute blood loss, provided that appropriate measures are taken to reduce potential risks and that additional studies are carried out’.1
Declaration of interest J. B.: chair of data safety monitoring board for international study of dexmedetomidine for Orion 2008 –9; honoraria paid to hospital charity. Member of scientific advisory board for Nestle; honoraria (if any) to be paid to hospital charity. Research grants from Health Foundation; NIHR Health Services Research & Delivery Programme; NIHR Research for patient Benefit Programme; EU Leonardo Programme. R.B.: consultancy fees from Gambro, Baxter, and Philips Medical. J.M.’s institution (the George Institute for Global Health, Sydney, Australia) has received travel expenses from Fresenius Kabi in relation to the development and conduct of an investigator-
595
Downloaded from http://bja.oxfordjournals.org/ by guest on April 11, 2015
R. Harika* K. Bermas C. Hughes A. Al-Khafaji M. Iyer D. J. Wallace Pittsburgh, USA * E-mail: [email protected]
Adverse effects of HES have been demonstrated in welldesigned investigator-initiated clinical trials in kidney donors,3 patients with sepsis,4 – 6 and in critically ill patients.7 Experimental and clinical studies strongly suggest that toxicity of HES can be attributed to tissue storage and coagulopathy. We ask the PRAC: what assumptions or clinical data would indicate that the same pathological mechanisms do not apply in patients with hypovolaemia from blood loss? Uptoone-thirdofappliedHESdosemaybestoredinthebodyin clinical settings,8 contributing to kidney3 – 7 or other organ injury,9 – 11 decreased survival in patients with sepsis,4 5 and causing pruritus.12 HES coagulopathy13 – 15 increases the risk of bleeding and need for blood and blood products in patients with sepsis,4 5 16 intensive care patients,7 those undergoing anaesthesia for major surgery,17 – 19 and after blunt trauma.20 The FDA issued a boxed warning for bleeding in cardiac surgical patients.21 It seems improbable that the PRAC recommendations ‘that HES solutions should not be used for more than 24 hours and that patients’ kidney function should be monitored for at least 90 days’ will guarantee patient safety. The adverse effects of HES appear to be generic to all HES classes22 23 and dose-dependent:4 5 7 no safe dose for HES has been defined.22 In CHEST, increased use of renal replacement therapy in intensive care patients occurred after an average dose of 5 ml kg21 day21, 1/10th of the maximal daily dose of 50 ml kg21.7 Monitoring kidney function for 3 months after the use of HES seems impractical, difficult to control, and of questionable impact on patient safety. The CRISTAL trial24 that may have contributed to the EMA’s new decision was not designed to assess the safety and efficacy of HES.25 As an open-label trial that combined various colloid or crystalloid fluids in the respective study arms, it does not provide sufficiently robust evidence to contradict the accumulated signal of harm emanating from all the other trials. If HES was a new drug, data from the CRISTAL study could not be included in the regulatory process for drug approval. Given the current safety concerns, it is hard to see why IRBs and patients would give approval or informed consent for further clinical trials, unless data from animal studies strongly suggest conditions where HES might be beneficial. The revised PRAC recommendation may mean that many thousands of patients with hypovolaemia and acute blood loss will continue to receive HES which will expose them to known risks of harm and offer no proven benefit.
Correspondence
weighing more than 100–150 kg. While surface landmarks may identify proper needle entry point, the tip may vary greatly as it traverses longer distances, as in the case of obesity. We would like to encourage the authors to use a technique that minimizes repositioning while maintaining the patient in a supine position, namely ilioinguinal/iliohypogastric nerve block. This type of block is ideal for the obese and muscular patients that may be augmented with mild to moderate sedation.
Declaration of interest None declared. C. Z. Kakazu* M. Lippmann California, USA * E-mail: [email protected]
doi:10.1093/bja/aeu028
Cardiac arrest after liver transplantation in a patient with takotsubo cardiomyopathy Editor—We report a patient, 52-yr-old male, with normal pretransplant cardiac workup who underwent orthotopic liver transplantation for end-stage liver disease due to haemochromatosis and alcohol use. The procedure was uncomplicated with a normal transoesophageal echocardiogram; however, the patient developed pulseless ventricular tachycardia after surgical closure. Cardiopulmonary resuscitation was performed with return of spontaneous circulation within 60 s. He was transferred to the intensive care unit (ICU) on amiodarone, norepinephrine, and vasopressin infusions. He was in sinus tachycardia 100–117 beats min21, with central venous pressure 14–16 cm H2O, pulmonary artery systolic pressure 38–42 cm H2O, and cardiac output 7–10 litre min21. Initial troponin level was 0.22 ng ml21 and electrocardiogram showed new anteroseptal Q waves with minimal ST elevation and lateral T wave inversions. Immediate bedside transthoracic echocardiogram exhibited mid-to-distal and apical akinesia. Basal segments exhibited preserved wall function, but overall ejection fraction remained 25%. Left heart catheterization was performed, which showed no arterial stenosis or occlusions. Takotsubo cardiomyopathy was diagnosed and vasopressors were changed to milrinone and phenylephrine. Troponin level peaked at 7.48 ng ml21 on postoperative day 1. The patient was extubated and weaned off milrinone and phenylephrine on postoperative day 5. Echocardiogram was unchanged on postoperative day 6 but showed normal cardiac function when repeated on postoperative day 18 (Fig. 1A – D). Meanwhile, liver function tests continually improved from the day of surgery, and the transaminases were normal by postoperative day 9.
594
Takotsubo cardiomyopathy, also known as transient apical ballooning syndrome, stress-induced cardiomyopathy, or ‘broken heart syndrome,’ gets its name from the Japanese word for ‘fishing pot for trapping octopus’, based on the pathological appearance of the left ventricle.1 It was first described in Japan over 20 yr ago and since then has been described in a variety of clinical scenarios. The most common pathological finding is focal myocytolysis. The cardiomyopathy is distinctive because the apical wall of the left ventricle is affected, but the base is spared. Some have proposed that the apex is more vulnerable due to its limited elasticity reserve from not having a three layered myocardial configuration.2 Moreover, the apex has a limited coronary circulation and its increased b-receptor density makes it more sensitive to adenylate stimulation. The most common characteristics are: predominant occurrence in elderly or post-menopausal women; ST elevation/depression or T wave changes; onset after an acute emotional stress or an acute medical condition; prolonged QT interval; akinesis of the apical and distal anterior wall and hypercontraction of the basal wall; mild increase in cardiac enzymes; complete resolution of apical wall motions abnormality and the depressed left ventricular systolic function.1 Cases of takotsubo cardiomyopathy have been reported in the setting of liver transplantation,3 but this is the first description presenting as cardiac arrest immediately after transplantation. Awareness of the condition and early echocardiographic
Downloaded from http://bja.oxfordjournals.org/ by guest on April 11, 2015
1 Mokini Z, Buccino G, Vitale G, Mauri T, Fumagalli R, Pesnti A. Psoas compartment block for anaesthesia during surgical repair of inguinal hernias. Br J Anaesth 2013; 111: 298– 9
Fig 1 (A) The left ventricle with mitral valves open, in mid-diastole. (B) The left ventricle in end systole, with mitral valves closed. (A) and (B) were obtained 20 min after cardiac arrest. (B) demonstrates apical ballooning, with preserved proximal contractility. (C) and (D) were obtained 17 days later. (C) The left ventricle with the mitral valves open, in mid-diastole. (D) The left ventricle with mitral valves closed, in end systole. There is now normal apical contractility and normal systolic function.
BJA
Correspondence
evaluation are imperative for making this diagnosis. The condition can have a good prognosis if diagnosed early and aggressive supportive management is initiated. The expanding use of point-of-care ultrasound in the ICU will likely lead to increased recognition of this condition.
Declaration of interest None declared.
Funding D.J.W. receives research support from the NIH (NHLBI-K12HL109068).
1 Wittstein IS, Thiemann DR, Lima JAC, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352: 539– 48 2 Mori HH, Ishikawa SS, Kojima SS, et al. Increased responsiveness of left ventricular apical myocardium to adrenergic stimuli. Cardiovasc Res 1993; 27: 192– 8 3 Tachotti Pires LJ, Cardoso Curiati MN, Vissoci Reiche F, et al. Stress-induced cardiomyopathy (takotsubo cardiomyopathy) after liver transplantation-report of two cases. Transplant Proc 2012; 44: 2497– 500
doi:10.1093/bja/aeu029
Open letter to the Executive Director of the European Medicines Agency concerning the licensing of hydroxyethyl starch solutions for fluid resuscitation Editor—We have sent this letter to the Executive Director of the European Medicines Agency: we are concerned that the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee’s (PRAC) recent conclusions on the use of hydroxyethyl starch (HES)1 will result in harm to patients. In June, the PRAC recommended the suspension of marketing authorization for HES, as the available evidence demonstrated that any possible benefits from HES no longer outweigh its risk.2 On October 11, 2013, the PRAC revised its conclusions, announcing that ‘HES must no longer be used to treat patients with sepsis or burns injuries or in critically ill patients because of an increased risk of kidney injury and mortality. HES solutions may, however, continue to be used in patients to treat hypovolaemia caused by acute blood loss, provided that appropriate measures are taken to reduce potential risks and that additional studies are carried out’.1
Declaration of interest J. B.: chair of data safety monitoring board for international study of dexmedetomidine for Orion 2008 –9; honoraria paid to hospital charity. Member of scientific advisory board for Nestle; honoraria (if any) to be paid to hospital charity. Research grants from Health Foundation; NIHR Health Services Research & Delivery Programme; NIHR Research for patient Benefit Programme; EU Leonardo Programme. R.B.: consultancy fees from Gambro, Baxter, and Philips Medical. J.M.’s institution (the George Institute for Global Health, Sydney, Australia) has received travel expenses from Fresenius Kabi in relation to the development and conduct of an investigator-
595
Downloaded from http://bja.oxfordjournals.org/ by guest on April 11, 2015
R. Harika* K. Bermas C. Hughes A. Al-Khafaji M. Iyer D. J. Wallace Pittsburgh, USA * E-mail: [email protected]
Adverse effects of HES have been demonstrated in welldesigned investigator-initiated clinical trials in kidney donors,3 patients with sepsis,4 – 6 and in critically ill patients.7 Experimental and clinical studies strongly suggest that toxicity of HES can be attributed to tissue storage and coagulopathy. We ask the PRAC: what assumptions or clinical data would indicate that the same pathological mechanisms do not apply in patients with hypovolaemia from blood loss? Uptoone-thirdofappliedHESdosemaybestoredinthebodyin clinical settings,8 contributing to kidney3 – 7 or other organ injury,9 – 11 decreased survival in patients with sepsis,4 5 and causing pruritus.12 HES coagulopathy13 – 15 increases the risk of bleeding and need for blood and blood products in patients with sepsis,4 5 16 intensive care patients,7 those undergoing anaesthesia for major surgery,17 – 19 and after blunt trauma.20 The FDA issued a boxed warning for bleeding in cardiac surgical patients.21 It seems improbable that the PRAC recommendations ‘that HES solutions should not be used for more than 24 hours and that patients’ kidney function should be monitored for at least 90 days’ will guarantee patient safety. The adverse effects of HES appear to be generic to all HES classes22 23 and dose-dependent:4 5 7 no safe dose for HES has been defined.22 In CHEST, increased use of renal replacement therapy in intensive care patients occurred after an average dose of 5 ml kg21 day21, 1/10th of the maximal daily dose of 50 ml kg21.7 Monitoring kidney function for 3 months after the use of HES seems impractical, difficult to control, and of questionable impact on patient safety. The CRISTAL trial24 that may have contributed to the EMA’s new decision was not designed to assess the safety and efficacy of HES.25 As an open-label trial that combined various colloid or crystalloid fluids in the respective study arms, it does not provide sufficiently robust evidence to contradict the accumulated signal of harm emanating from all the other trials. If HES was a new drug, data from the CRISTAL study could not be included in the regulatory process for drug approval. Given the current safety concerns, it is hard to see why IRBs and patients would give approval or informed consent for further clinical trials, unless data from animal studies strongly suggest conditions where HES might be beneficial. The revised PRAC recommendation may mean that many thousands of patients with hypovolaemia and acute blood loss will continue to receive HES which will expose them to known risks of harm and offer no proven benefit.
