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of gene-expression profiling to assess cancer prognosis and guide therapy; on the sidelines, we may very well find ourselves in the scientific the use of genotyping to stratify patients according to the risk of a disease, “reruns” instead of at the forefront of novel, cutting-edge research.
such as prolonged QT interval syndrome or myocardial infarction; the use Stephan Ziegeler, M.D., Byron E. Tsusaki, D.O., Charles D.
of genotyping to increase our understanding of drug pharmacokinetics Collard, M.D.* *University of Texas Health Science Center at Houston
and pharmocodynamics; and the use of genetics for tissue engineering and Baylor College of Medicine, and Texas Heart® Institute, St. Luke’s and the cloning of several different species.1–4 Recently, the National Episcopal Hospital, Houston, Texas. [email protected] Human Genome Research Institute announced the formation of the In-ternational HapMap project, which will attempt to improve the ease andaccuracy of human genetic risk profiling by creating a haplotype map References
consisting of approximately 500,000 tag single nucleotide polymorphisms 1. Sullenger BA: Targeted genetic repair: An emerging approach to genetic from the more than 10 million that exist within the human genome. Even therapy. J Clin Invest 2003; 112:310 –1 in diseases such as Huntington chorea, in which identification of the 2. Guttmacher AE, Collins FS: Welcome to the genomic era. N Engl J Med specific causative mutation has yet to lead to improved treatment, patients 3. Burke W: Genomics as a probe for disease biology. N. Engl J Med 2003; and their families have benefited from genetic counseling.5 All of these mind-boggling accomplishments have occurred within a single 4. Collins FS, Green ED, Guttmacher AE, Guyer MS: A vision for the future of genomics research. Nature 2003; 422:835– 47 Is perioperative functional genomics ready for prime time? Maybe 5. Hogarth P: Huntington’s disease: A decade beyond gene discovery. Curr not quite yet. But one thing is assured: If genetic advances continue tooccur at the current rate and the discipline of anesthesiology remains (Accepted for publication October 29, 2003.) 2004 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.
Base Excess and Strong Ion Difference: Clinical Limitations To the Editor:—The problem of method-related errors, arising from Table 1. Normal Values for the Base Excess (BE) from Venous
different measuring technologies on calculation of the anion gap and Blood (n ؍ 50)
the strong ion difference, was clearly demonstrated in patients in arecent study by Morimatsu et al.1 Mean values differed significantly, in some cases leading to a diverging assessment of the acid-base or electrolyte status. To a clinician, however, this is not acceptable.
All quantities, including the base excess (BE), used for diagnosis of nonrespiratory acid-base disturbances (e.g., metabolic, renal, or intes- tinal) are calculated quantities. Hence, each quantity must be assessed for reliability and associated diagnostic interpretation (normal rangeand normal values: mean Ϯ SD; pathologic range). This greatly de- * BE is calculated from measured venous pH, PCO , S pends on the inaccuracy and imprecision of each of the measured PCO ϭ partial pressure of carbon dioxide; P primary values used in the particular calculation and on how these are propagated. BE is usually obtained with arterial blood from measuredpH, partial pressure of carbon dioxide (PCO ), and hemoglobin-con- Medical Association (Bundesärztekammer 2002, Köln, Germany) for centration in a blood gas analyzer, the strong ion difference from the electrolyte concentrations in the plasma are Na 142 Ϯ 2.8 mmol/l measured plasma electrolyte concentrations (e.g., Na, K, Cl, lactate).
(2.0%); K 4.5 Ϯ 0.2 mmol/l (3.7%); Cl 103 Ϯ 4.1 mmol/l (4%); and For clinical practice, we propose the whole blood BE, which should lactate 1.5 Ϯ 0.1 mmol/l (6%). Using these figures, the normal value be preferably used depending on the following considerations: of the strong ion difference (Na ϩ K Ϫ Cl Ϫ lactate) is calculated as Inaccuracy of calculated BE: If correctly calculated, BE can be
42 Ϯ 5.0 mmol/l, with high inaccuracy from propagation of errors.
obtained from measured pH, PCO , oxygen saturation, and total hemo- Hence, reliability is strongly reduced, dominated by the largest errors globin in any blood sample (venous or arterial). Over the whole range (Na: Ϯ 2.8 mmol/l; Cl: Ϯ 4.1 mmol/l).
(Ϫ30 to ϩ30 mmol/l), mean inaccuracy is less than 1 mmol/l.2 In comparison, normal BE is 0 Ϯ 2.2 mmol/l when calculated from Normal values for BE and variability: Normal values for BE in
normal values of pH 7.40 Ϯ 0.02, PCO 40 Ϯ 1.6 mmHg (4%), hemo- arterialized capillary blood of men (n ϭ 20) are Ϫ0.1 Ϯ 1.2 mmol/l, globin 15 Ϯ 0.3 g/dl (2%), and full oxygen saturation ف 100%. Reli- and of women (n ϭ 20), Ϫ1.0 Ϯ 1.1 mmol/l.3 Variability of BE in ability of BE is mainly affected by the inaccuracy of measurement for healthy individuals is very low and could be reproduced if calculated pH and PCO , whereas that for hemoglobin is negligible.
also from measurement in venous blood. Typical results (mean Ϯ SD) BE as a prognostic factor: The diagnostic use and prognostic value
as obtained with blood from the vena cubitalis (50 healthy volunteers: of BE is well documented. Among 10 clinical hemodynamic and 20 colleagues and medical students) are shown in Table 1. Values for pH, blood laboratory parameters tested, change in BE proved to be the best PCO , partial pressure of oxygen, and oxygen saturation were measured predictor of blood volume changes in a canine hemorrhagic shock in a blood gas analyzer (AVL OMNI 9; Roche Diagnostics, Mannheim, model.4 In critically ill patients BE has been established as an indepen- Germany), calibrated with two precision buffers for pH (Radiometer dent predictor of mortality5 and endpoint of resuscitation. On the basis phosphate buffer S 1500; S 1510), and the mean calculated BE was Ϫ0.1 of 8,200 polytrauma patients, statistically selected out of 15,200 from Ϯ 1 mmol/l. It should be noted that the SD of BE is still low, even though four clinical studies, mortality increased significantly with a decrease in measured values used in the calculation varied largely (Table 1).
BE, e.g., approximately by 25% if the assessed BE was Ϫ6 mmol/l Tolerable values of inaccuracy: Representative normal values
within the first 24 h after admission (see figure 4 in reference 6).6 and maximal inaccuracy of the measured acid-base and electrolyte Conclusions: Because mortality may increase considerably (ف 8%)
variables in blood, as tolerated by the recommendations of the German when BE is decreased by only 2 mmol/l, the clinical requirements for reliability (inaccuracy, imprecision) should be high (Յ 2 mmol/l). By 2. Lang W, Zander R: The accuracy of calculated base excess in blood. Clin using present standard measuring technology, this is met only for the 3. Lentner C: Physical chemistry, blood, somatometric data, Geigy Scientific BE and not for the strong ion difference or lactate alone. The latter Tables, volume 3. Edited by Lentner C. Basel, Ciby-Geigy Limited, 1984, p 73 should be used only as secondary parameters in combination with the 4. Waisman Y, Eichacker PQ, Banks SM, Hoffman WD, MacVittie TJ, Natanson BE for a differential diagnosis, e.g., nonrespiratory acidosis correlated C: Acute hemorrhage in dogs: Construction and validation of models to quantify to lactate, hyperchloremia, or anion gap.7 blood loss. J Appl Physiol 1993; 74:510 –19 5. Neugebauer E, Zander R: Clinical relevance of base excess and lactate Rolf Zander, Prof. Dr. med. Werner Lang, Dr. rer. nat.*
concentration (editorial). Anästhesiol Intensivmed Notfallmed Schmerzther *Institut für Physiologie und Pathophysiologie, Johannes Gutenberg- Universität Mainz, Mainz, Germany. wlang@uni-mainz 6. Zander R: Diagnostische und therapeutische Bedeutung von Base Excess und Lactatkonzentration. Anästhesiol Intensivmed Notfallmed Schmerzther References
7. Brill SA, Stewart TA, Brundage SI, Schreiber MA: Base deficit does not predict mortality when secondary to hyperchloremic acidosis. Shock 2002; 1. Morimatsu H, Rocktäschel J, Bellomo R, Uchino S, Goldsmith D, Gutteridge G: Comparison of point-of-care versus central laboratory measurement of elec-trolyte concentrations on calculations of the anion gap and the strong iondifference. ANESTHESIOLOGY 2003; 98:1077– 84 (Accepted for publication September 6, 2003.) 2004 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.
Alternative Formula for Laryngeal Mask Airway™ Size Selection To the Editor:—Size selection of the Laryngeal Mask Airway™ is similar to the sex-based LMA™ size recommendation for adult (LMA™; Laryngeal Mask Company Limited, San Diego, CA) is impor- tant for avoiding complications and is based on patient body weight.1 Our formula is convenient for pediatric patients, although it cannot The previously proposed formula for determining the appropriate be used in infants weighing less than 5 kg. In addition, the formula LMA™ size2 is impractical because it contains the square root of the does not require a pocket calculator.
patient’s body weight. We advocate here an alternative formula: Nakamura,
Nobuhiro
LMA™ size ϭ 1 ϩ BWru/20, where BWru indicates body weight (in Maekawa, M.D. * Kagawa Medical School, Kagawa, Japan.
kilograms) rounded up at the first digit. For example, if a patient’s body weight of 14 kg (BWru) is 20 because 14 can be rounded up to 20 atthe first digit, the calculation would be as follows: LMA™ size ϭ 1 ϩ References
If the calculation of LMA™ size shows 3.5 or 4.5, we choose LMA™ 1. Brimacombe JR, Brain AIJ: Preparation for use, The Laryngeal Mask Airway: #3 or #4. This manner of size selection agrees with the recommenda- A Review and Practical Guide. Edited by Brimacombe JR, Brain AIJ, London, tion by Brimacombe and Brain.1 Alternatively, if the calculated LMA™ size is 3.5 or 4.5, we can also use LMA™ #4 or #5. This size selection 2. Kagawa T, Obara H: An easy formula to remember the laryngeal mask airway size-patient weight relationship. ANESTHESIOLOGY 2000; 92:631–2 3. Brimacombe JR, Berry AM, Campbell RC, Verghese RC: Selection of proper size of laryngeal mask airway in adults. Anesth Analg 1996; 83:664 Support was provided solely from institutional and/or departmental sources.
(Accepted for publication June 20, 2003.) 2004 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.
Delayed Postoperative Arousal following Remifentanil-based Anesthesia in a Myasthenic Patient Undergoing Thymectomy To the Editor:—Remifentanil (Ultiva; GlaxoSmithKline, Middlesex, UK) Premedication was limited to 0.2 mg intramuscular glycopyrrolate is an “ultra-short”–acting opioid that is rapidly hydrolyzed by circulat- and1 mg intravenous midazolam. Anesthesia was induced with100 mg ing and tissue nonspecific esterases. Discontinuation of remifentanil lidocaine and 2 mg/kg propofol intravenously, to be followed by 3.0 infusion will be followed by a rapid recovery regardless of the duration ␮g/kg remifentanil over 30 s, and tracheal intubation. Anesthesia was of infusion.1 The present report used the remifentanil-based technique maintained by sevoflurane 1–2% in 100% oxygen, supplemented with of anesthesia, without the use of muscle relaxants, in a myasthenic remifentanil infusion (0.1– 0.25 ␮g · kgϪ1 · minϪ1). Neuromuscular gravis patient undergoing transternal thymectomy. However, the pa- transmission was monitored by electromyography using a Datex rel- tient manifested unexpected delay of postoperative arousal for 12 h.
axograph (NMT-100 –23– 01; Datex-Ohmeda Division, Instrumentar- This is the first case report about a significant delay of postoperative ium Corp, Helsinki, Finland), using the electromyographic response to arousal following discontinuation of remifentanil infusion.
ulnar nerve stimulation by the train-of-four. Intraoperatively, blood A 19-yr-old female patient (body weight, 57 kg) presented with pressure ranged between 75/30 mmHg and 105/55 mmHg, heart rate myasthenia gravis (Osserman 2A) associated with a thymoma. Pyri- ranged between 55 and 90 bpm, and electromyography showed nor- dostigmine, 60 mg, four times daily was administered for 2 months, to mal T1/control and T4/T1 ratios. The duration of surgery was 2 h.
be followed by transternal thymectomy. The pyridostigmine regimen Thirty minutes before the end of surgery, 5 mg intramuscular mor- was maintained until the morning of surgery.
phine was administered. Twenty minutes before the end of surgery,sevoflurane was turned off, and on completion of surgery remifentanilinfusion was discontinued. The total dose of remifentanil administered Support was provided solely from institutional and/or departmental sources.
throughout surgery amounted to about 2,000 ␮g.

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