LOW HEMOGLOBIN LEVELS DURING NORMOVOLEMIA ARE ASSOCIATED WITH ELECTROCARDIOGRAPHIC CHANGES IN PIGS Bertram Scheller,* Gordon Pipa, †‡ Harry Kertscho,* Patrick Lauscher,* Joachim Ehrlich, § Oliver Habler, || Kai Zacharowski,* and Jens Meier* *Clinic for Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt; † Department of Neurophysiology, Max Planck Institute for Brain Research; ‡ Frankfurt Institute for Advanced Studies, Johann Wolfgang Goethe University; § Division of Cardiology, Department of Medicine, University Hospital Frankfurt; and || Clinic for Anesthesiology, Intensive Care Medicine and Pain Therapy, Hospital Nordwest, Frankfurt, Germany Received 19 Apr 2010; first review completed 10 May 2010; accepted in final form 4 Aug 2010 ABSTRACT—We studied whether low hemoglobin concentrations during normovolemia change the myocardial electrical current (electrocardiogram) in a pig model. Normovolemic anemia was achieved by stepwise replacing blood with colloids (hydroxyethyl starch 6%). We measured the length of the PQ-, QT-, QTc, and the ST interval as well as the amplitude of the Q wave and T wave at hemoglobin concentrations of 9.5, 8.0, 5.5, 3.8, and 3.3 gIdL j1 . Normovolemic anemia is accompanied by a gradual prolongation of the QT and QTc interval and a reduction in the amplitude of the T wave. The QRS complex is partly diminished in amplitude. Results were verified performing a time-frequency analysis on single heartbeats. During severe anemia and normovolemia, electrocardiographic changes can be detected. Further investigations are warranted to elucidate whether these changes indicate myocardial hypoxia. KEYWORDS—ECG, normovolemia, anemia, QT prolongation, T wave, hemoglobin INTRODUCTION Blood loss is common during surgery; however, severe anemia is usually treated with transfusion of red blood cells. Whether transfusion is carried out, normovolemia is man- datory at all times. Electrocardiogram (ECG) monitoring is implemented as a fixed element in the perioperative period. Electrocardiogram is easily accessible and noninvasive. Clinically, the ECG is used to monitor the heart rate (HR) and the occurrence of arrhythmias. Furthermore, ECG signals pro- vide information regarding ischemic conditions of the heart. In contrast to myocardial ischemia and myocardial infarction, the depression or elevation of the ST segment as a marker pointing toward acute myocardial tissue hypoxia has been shown to be of little sensitivity and specificity during acute isovolemic anemia (1). However, within the last decades, clin- ical outcome studies revealed the prognostic value of other subtle changes in the ECG with respect to mortality (2Y8). For example, prolongation of the QT interval and depression of the ST segment, as well as changes in HR variability and T-wave alternans, occur in chronic diseases with an increase in mortality (9Y12). It is unknown whether similar ECG changes also occur during acute normovolemic anemia and may indicate a critical restriction of oxygen transport, tissue oxygenation, and by that imminent tissue hypoxia. One might speculate that during progressing anemia, typical, subtle ECG changes appear be- fore the individual critical hemoglobin (Hb) concentration has occurred. We hypothesized that a low Hb concentration (Hb crit ) during normovolemia may cause alterations of the myocardial elec- trical current in a concentration-dependent fashion. Therefore, we investigated the impact of gradually increasing normovol- emic anemia in an experimental setting on the descriptors of single-heartbeat traces of the ECG. MATERIALS AND METHODS Study design After governmental approval, data were collected from eight healthy pigs (Deutsches Edelschwein) of either sex (female, n = 4; male, n = 4), weighing between 25 and 29 kg (mean body weight, 26.4 T 1.2 kg). Animals were treated in accordance with the Principles of Laboratory Animal Care (National Insti- tutes of Health publication 86-23, 1985). Anesthesia Food was withheld for one night, but there was free access to water. Intra- muscular premedication was performed using midazolam (2 mgIkg j1 ) and ket- amine (10 mgIkg j1 ). Anesthesia was induced by intravenous injection of fentanyl (0.01 mgIkg j1 ), propofol (4 mgIkg j1 ), and vecuronium bromide (0.3 mgIkg j1 ) and maintained by continuous infusion of fentanyl (0.02 mgIkg j1 I h j1 ) and propofol (20 mgIkg j1 Ih j1 ). Muscular relaxation was maintained by continuous infusion of vecuronium bromide (1 mgIkg j1 Ih j1 ) to minimize any potential disturbances of the ECG recordings. Estimated insensible fluid losses other than those of blood withdrawal (e.g., perspiration, etc.) were compensated by intravenous infusion of Ringer’s solution (3 mLIkg j1 Ih j1 ). A warming unit (Mallinckrodt WarmTouch 5200; Mallinckrodt Medical, Hazelwood, Mo) was used to maintain the body tem- perature constant at 36-C T 0.5-C. Pigs were endotracheally intubated and mechanically ventilated at a rate of 12 min j1 and a positive end-expiratory pressure of 5 cm H 2 O (intermittent positive pressure ventilation). Tidal volume was adjusted to maintain normocapnia (36Y40 mmHg), which was confirmed on the basis of multiple blood gas analyses. Instrumentation and monitoring All animals were placed in supine position. Several catheters were inserted using Seldinger technique to minimize blood loss. A 20-gauge catheter was placed into the left femoral artery for continuous arterial pressure recording and 375 SHOCK, Vol. 35, No. 4, pp. 375Y381, 2011 Address reprint requests to Bertram Scheller, MD, MSc, Clinic for Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. E-mail: scheller@em.uni- frankfurt.de. G.P. is funded by the Hertie Foundation, Frankfurt, Germany. J.M. is funded by the Else-Kro ¨ner Fresenius Foundation, Bad Homburg, Germany. The authors declare that they have no conflicts of interest. DOI: 10.1097/SHK.0b013e3181f6aa44 Copyright Ó 2011 by the Shock Society Copyright © 2011 by the Shock Society. Unauthorized reproduction of this article is prohibited.