Journal of Clinical Anesthesia (2007) 19,92–96

Original contribution The importance of blood sampling site for determination of and biochemistry values in major abdominal and orthopedic surgery

Shmuel Evron MD (Senior Lecturer)a,g,1, Vladimir Tress MD (Orthopedic Surgeon)b,1, Tiberiu Ezri MD (Senior Lecturer)a,g,1, Peter Szmuk MD (Associate Professor)f,g,*, Ofer Landau MD (Lecturer)c,1, David Hendel MD (Senior Lecturer)b,1, Pinhas Schechter MD (Senior Lecturer)d,1, Benjamin Medalion MD (Lecturer)e,1 aDepartment of Anesthesia, Edith Wolfson Medical Center, Holon 58100, Israel bDepartment of Orthopedics, Edith Wolfson Medical Center, Holon 58100, Israel cDepartment of Surgery ‘‘B’’, Edith Wolfson Medical Center, Holon 58100, Israel dDepartment of Surgery ‘‘A’’, Edith Wolfson Medical Center, Holon 58100, Israel eDepartment of Cardiothoracic Surgery, Beilinson Medical Center, Petah Tikva, Israel fDepartment of Anesthesiology, University of Texas Medical School at Houston, Houston, TX 77030, USA gDepartment of Outcomes Research Institute, University of Louisville, Louisville, KY, USA

Received 17 April 2006; accepted 21 April 2006

Keywords: Abstract Blood hemoglobin and Study Objective: To determine whether sampling of blood from different sites influences laboratory biochemistry; results. Sampling sites; Design: Prospective, double-blind study. General anesthesia; Setting: University-affiliated hospital in Israel. Surgery Patients: 100 ASA physical status I, II, and III patients undergoing major orthopedic or colon surgery (total hip and revision of total hip replacement, colon resection, or radical cystectomy). Measurements: Blood was sampled simultaneously for hemoglobin, electrolytes, glucose, pH, blood gases, and lactate from three sampling sites (peripheral vein, central vein, and radial ) at 5 time frames (after induction of anesthesia [baseline], one hr after induction of anesthesia, at the end of surgery, after one hr in the recovery room, and 4 hrs after surgery). At the same time points, recorded rectal temperature, mean arterial pressure, rate, and central venous pressure were recorded. Anesthesia, monitoring, and dwell volumes before sampling were standardized. Main Results: There were no significant differences between the results of hemoglobin, electrolytes, glucose, pH, and blood gases obtained from different sampling sites and at different time frames. Lactate level (mmol/L) was higher in peripheral than it was in either the central vein or radial

* Corresponding author. Department of Anesthesiology, University of Texas Medical School at Houston, Houston, TX 77030, USA. Tel.: +1 713 661 5401; fax: +1 713 500 6201. E-mail address: [email protected] (P. Szmuk). 1 Affiliated with the Sackler School of Medicine, Tel Aviv, Israel.

0952-8180/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2006.04.005 Sampling sites for laboratory analyses 93

artery (b0.05), and higher in central venous blood compared with arterial blood ( P b 0.05; 2.04 F 1.16, 1.74 F 0.78, and 1.54 F 0.68, respectively). Conclusion: Under stable hemodynamics and in the absence of hypothermia, serum lactate level was higher in peripheral venous blood than it was in the central vein or radial artery. D 2007 Elsevier Inc. All rights reserved.

1. Introduction Each patient served as his or her own control. The patients were connected to the standard ASA monitors, and The effect of sampling site on the measured values of a 16-gauge intravenous (IV) catheter was inserted in the various laboratory analyses has been questioned repeatedly antecubital vein (peripheral vein). After induction of in previous publications. Laboratory measurement values anesthesia with propofol, fentanyl, rocuronium, and iso- may vary between different sampling sites. It is well known flurane, central venous catheters via the right internal that laboratory tests results obtained from capillary sampling jugular vein and radial artery catheters were placed. The via a percutaneous puncture may be different from those central line catheters were not heparin-coated. If the taken from peripheral venous and arterial samples, possibly insertion of one of these three catheters (large peripheral owing to the mechanical and chemical effects during the vein, central vein, or arterial cannula) failed, the case was sampling process [1-4]. Other authors have found no such a excluded from the study. As per routine, after surgery, a difference [5,6]. chest radiograph was performed in the recovery room to Further controversy on this topic is provided by Johnson confirm the correct placement of the central venous catheter et al [7], who showed that intraosseous and central venous within the superior vena cava. If the catheter was incorrectly blood biochemical and hemoglobin (Hb) values were placed (ie, in the subclavian vein), the case was subse- similar during hemodynamic stability and throughout quently excluded from the study. A second peripheral vein 30 minutes of resuscitation if no drugs were given through was used for fluid administration. the intraosseous site. However, differences existed after The blood sample was drawn in preheparinized syringes 30 minutes of cardiopulmonary resuscitation and infusions and analyzed immediately in our OR laboratory. Blood was through the intraosseous site. The authors concluded that obtained for Hb and blood chemistry (glucose, sodium, laboratory values may be erroneous when intraosseous potassium, lactate, pH, and blood gases). The samples were blood is used during periods of resuscitation lasting longer analyzed with the GEM Premier 3000 blood gas and than 5 minutes and if drugs and fluid boluses have also been electrolytes analyzer (Model 5700, GMI, Inc, Ramsey, infused through this site [7]. MN). Blood sampling was performed simultaneously from Because there are certain clinical situations in anesthesia the three sampling sites at 5 time points during the (ie, perioperative hypovolemia) where biochemical meas- perioperative period: after induction of anesthesia (baseline), urements (ie, blood lactate level) must be tracked closely one hour after induction of anesthesia, at the end of surgery, and clinical decisions are affected by such readings, it is after one hour in the recovery room, and 4 hours after important to make the monitoring of these data more valid. surgery. Arterial oxygenation (Pao2) was measured while the Our hypothesis was that sampling of blood from different patient was receiving an inspired oxygen concentration sites might have an influence on laboratory test results. (Fio2) of 0.30. Arterial carbon dioxide concentration (Paco2) was measured while the patient was ventilated 2. Materials and methods 10 breaths a minute with a tidal volume of 8 mL/kg. Mean arterial pressure (MAP), heart rate (HR), central venous After obtaining approval from Edith Wolfson Medical pressure (CVP), and urine output (UO) were also recorded at Center institutional review board for the study, and written, the same time frames. The blood was obtained from a informed consent from patients, some 100 patients under- stopcock connected to the vein/artery through an extension going major surgeries (total hip and revision of total hip tube (15-cm microspace pressure monitoring line; Biometrix replacement, colon resection, and radical cystectomy) with Israel, Ltd, Jerusalem, Israel), and for the sampling from the general anesthesia that required peripheral, central venous, central catheter, the stopcock was directly connected to the and arterial catheterization, were recruited to this prospec- distal lumen of a double-lumen catheter. Volume of the dwell tive, double-blind study. These surgeries were chosen for (bdeadQ) space volume of the extension + stopcock was study because they are the most frequently encountered 0.4 mL, whereas the volume of the distal lumen of the major surgeries in our operating room (OR). We did not 7-French double-lumen catheter (Vygon, Ecouen, France) include liver and cardiac surgeries because of their was 0.56 mL (0.4 mL + plus the stopcock 0.16 mL). All propensity to affect lactate levels by producing regional or blood samples were obtained from catheters after discarding systemic low perfusion states. Patients with known hemo- the first 10 mL (N5 times tubing and cannula bdead spaceQ lytic disorders were also excluded from the study. vol) of blood from each site [8]. For each patient, the total 94 S. Evron et al.

analysis for analysis of variance was performed. A repeated- Table 1 Demographic data and intraoperative fluid balance measure general linear analysis with Bonferroni adjustment F Variable Mean SD or was used to evaluate the between-subjects effects. median (range) We also performed a multivariable analysis with repeat- Age (y) 68.5 F 11 ed-measure general linear models. Primary outcome was ASA physical status II (I-III) difference in lactate levels between sampling sites (during F Surgery time (min) 172 85 all time point measurements). The effects of type of surgery, Rectal temperature (8C) 36.2 F 0.8 total fluid administered, age, gender, and patient’s body Average intraoperative UO (mL/h) 110 F 40 Blood loss (mL) 404 F 271 mass index on the primary outcome variable were studied. Fluid input (mL) 3480 F 1089 Data analysis was performed using the SPSS for Windows Blood transfused (mL) 150 F 90 (SPSS, Inc, Chicago, IL). Statistical significance was achieved when P value is less than 0.05. amount of sampled blood was 165 mL [10 mL discard  15 samplings (5 time sampling points  3 sampling sites) + 3. Results (one mL blood for analysis  15 samplings)]. This volume o co was replaced by lactated Ringer’s solution in a ratio of 3 mL Results are presented in Tables 1, 2, and 3.Pa 2,Pa 2, for each milliliter of blood lost by the patient. The UO, HR, MAP, CVP, and rectal temperature did not change appropriate volume was replaced after each sampling. significantly at different sampling time points (Table 2). The arterial catheter and central and peripheral veins Table 3 presents laboratory results from the three sampling dedicated to blood sampling were flushed with a 0.9 NaCl sites at different sampling time points. Only the serum solution containing 2 IU/mL heparin at a rate of 1.2 mL/h. lactate values changed significantly among the three sam- The flushing system was placed near the sampling stopcock. pling sites, but there was no correlation with the sampling The continuous flushing was stopped two minutes before time. Lactate level (mmol/L) was higher in peripheral venous each sampling. An independent researcher who was unaware blood than it was in the central vein or artery (b0.05) and of the sample site from which the blood was drawn analyzed higher in central venous blood than in arterial blood (2.04 F all the blood samples. Intraoperatively, all patients received 1.16, 1.74 F 0.78, and 1.54 F 0.68, respectively; P b 0.05). lactated Ringer’s solution at a rate of 10 mL kgÀ1 hÀ1 plus Multivariable regression analysis did not reveal any replacement of ongoing blood loss as required. effect of the type of surgery, total fluid administered, age, Postoperatively, patients were given lactated Ringer’s gender, or patient’s body mass index on the primary solution at a rate of 100 mL/h. Cell savers were not used. outcome variable (lactate levels) studied. Patients were kept normothermic with fluid/blood warmers and forced-air warmers. Rectal temperature was monitored throughout the procedure. All patients had an indwelling 4. Discussion urinary bladder catheter. In this study, sampling of blood from three different sites 2.1. Data analysis in major surgical procedures resulted in significant differ- ences in serum lactate values. Our results clearly showed a Data are presented as means F standard deviation for higher lactate level in the peripheral venous sample continuous variables and as number of occurrences (per- compared with the other two sample sites, and a higher centage) or median (range) for noncontinuous variables. To lactate level in central venous blood as compared with calculate the necessary sample size for the study, a power arterial blood.

Table 2 Time-related oxygenation, ventilation, hemodynamics, and temperature Variable Sampling timesa 12345P

Pao2 (mmHg) 128 F 15 133 F 22 131 F 18 130 F 20 122 F 13 0.7 Paco2 (mmHg) 38 F 635F 337F 439F 436F 6 0.2 Urinary output (mL/h) 115 F 40 105 F 50 110 F 40 105 F 40 115 F 30 0.5 MAP (mmHg) 110 F 10 92 F 15 98 F 20 115 F 25 110 F 15 0.5 HR (bpm) 78 F 12 72 F 20 76 F 12 82 F 15 80 F 20 0.7 CVP (mmHg) 12 F 610F 414F 614F 412F 5 0.2 Temperature (8C) 36.4 F 0.9 36.3 F 0.9 36.1 F 0.8 36 F 0.7 36.2 F 0.7 0.5 Results are expressed as means F SD. CVP = central venous pressure. a Sampling times: 1 = before anesthesia (baseline); 2 = 1 hour after induction of anesthesia; 3 = end of surgery; 4 = after 1 hour in the recovery room; 5 = 4 hours after surgery. apigstsfrlbrtr analyses laboratory for sites Sampling

Table 3 Laboratory tests results from three sampling sites Variable Sampling time and site Baseline 1 h intraoperative End of surgery 1 h in the PACU 4 h in the PACU Peripheral Central Arterial Peripheral Central Arterial Peripheral Central Arterial Peripheral Central Arterial Peripheral Central Arterial Hemoglobin (g/dL) 12.3 F 1.6 12.1 F 1.7 12.2 F 1.6 11.5 F 2.1 11.8 F 1.5 11.8 F 1.6 11.5 F 1.3 11.5 F 1.3 11.5 F 1.3 11.3 F 1.2 11.3 F 1.1 11.4 F 1.2 11.4 F 1.2 11.3 F 1.2 11.3 F 1.2 Glucose (mg/dL) 123 F 28 122 F 36 122 F 40 136 F 37 131 F 39 133 F 39 137 F 28 135 F 27 135 F 29 136 F 29 129 F 27 130 F 31 133 F 25 129 F 25 129 F 28 Sodium (mEq/L) 138 F 4 136 F 13 138 F 4 137 F 4 137 F 4 137 F 4 137 F 4 138 F 3 137 F 4 137 F 4 138 F 11 137 F 3 137 F 4 137 F 4 137 F 4 Potassium (mEq/L) 4 F 0.7 3.8 F 0.6 3.8 F 0.6 4 F 0.7 3.8 F 0.5 3.8 F 0.5 4 F 0.5 4 F 0.5 3.9 F 0.5 4.1 F 0.5 4 F 0.5 3.9 F 0.5 4.1 F 0.5 4.1 F 0.4 4 F 0.5 pH 7.38 F 0.05 7.37 F 0.06 7.39 F 0.06 7.37 F 0.05 7.37 F 0.06 7.38 F 0.05 7.33 F 0.03 7.36 F 0.05 7.36 F 0.05 7.29 F 0.07 7.37 F 0.06 7.38 F 0.08 7.37 F 0.06 7.37 F 0.05 7.37 F 0.05 Lactate (mmol/L) 1.9 F 1 1.7 F 0.9 1.4 F 0.7 1.8 F 1 1.5 F 0.8 1.4 F 0.7 2.2 F 1.5 1.8 F 0.7 1.6 F 0.7 2.2 F 1.3 1.9 F 0.8 1.7 F 0.7 2.1 F 1.1 1.8 F 0.7 1.6 F 0.6 Mean overall Peripheral 2.04 F 1.16* lactate value Central 1.74 F 0.78* (mmol/L) Arterial 1.54 F 0.68* Results are expressed as means F SD. * P b 0.05. 95 96 S. Evron et al.

Some studies found no difference in the lactate levels Because there are certain clinical situations where the sampled from the central vein, pulmonary artery or arterial lactate levels are tracked closely and clinical decisions are site, in hemodynamically stable but critically ill patients affected by such readings, we recommend that once lactate [8-11]. Others found an arteriovenous lactate level discrep- sampling is started from a certain sampling site (preferably ancy [12] or reported that lactate level may be higher in blood arterial), it should be continued from the same site to render collected from the inferior vena cava [13]. Lavery et al [14] interpretation of the laboratory results more reliable. showed a high correlation between arterial and peripheral venous lactate levels in trauma patients. However, Gallagher et al [15] suggested that caution be used in the routine References substitution of venous as compared with arterial lactate. The reason for these differences is unclear. Sound [1] Ellison JM, Stegmann JM, Colner SL, et al. Rapid changes in explanations for our finding may be differences in regional postprandial blood glucose produce concentration differences at finger, forearm, and thigh sampling sites. Diabetes Care 2002; organ perfusion and/or peripheral venous vasoconstriction 25:961-4. as causative factors. [2] Peled N, Wong D, Gwalani SL. Comparison of glucose levels in In view of our findings, we support the opinion of capillary blood samples obtained from a variety of body sites. Gallagher et al [15], that caution should be used in the Diabetes Technol Ther 2002;4:35-44. routine substitution of venous as compared with arterial [3] Thurlbeck SM, McIntosh N. Preterm blood counts vary with sampling site. Arch Dis Child 1987;62:74-5. lactate. [4] Yang ZW, Yang SH, Chen L, Qu J, Zhu J, Tang Z. Comparison of In spite of these statistical differences, the biological blood counts in venous, fingertip and arterial blood and their significance of these findings is uncertain at low lactate measurement. Clin Lab Haematol 2001;23:155-9. levels, such as those encountered in our patients. However, [5] Carlson KK, Snyder ML, LeClair HW, Underhill SL, Ashwood ER, such a 20% difference between the arterial and venous Detter JC. Obtaining reliable plasma sodium and glucose determi- nations from pulmonary artery catheters. Heart Lung 1990;19:613-9. lactate levels may be important at higher, pathological [6] Flohr JA, Womack CJ, Kovalcik PC. Comparison of capillary and lactate levels. venous blood lactate and glucose values during cycle ergometry. The time of sampling did not influence this trend because J Sports Med Phys Fitness 1996;36:261-4. all the factors that might have adversely affected serum [7] Johnson L, Kissoon N, Fiallos M, Abdelmoneim T, Murphy S. Use of lactate (oxygenation, ventilation, temperature, fluid balance, intraosseous blood to assess blood chemistries and hemoglobin during cardiopulmonary resuscitation with drug infusions. Crit Care Med and patient’s hemodynamic and volume status as reflected 1999;27:1147-52. by UO, CVP, MAP, and HR) did not differ over time. [8] Jackson EV Jr, Wiese J, Sigal B, et al. Effects of crystalloid solutions The lack of differences among other laboratory param- on circulating lactate concentrations: part 1. Implications for the eters may be explained in part by the hemodynamic stability, proper handling of blood specimens obtained from critically ill normovolemia, normothermia, and normal oxygenation and patients. Crit Care Med 1997;25:1840-6. [9] Weil MH, Michaels S, Rackow EC. Comparison of blood lactate ventilation throughout surgery and the immediate postoper- concentrations in central venous, pulmonary artery, and arterial blood. ative period. On the other hand, the lack of hemodynamic Crit Care Med 1987;15:489-90. changes and hypothermia may strengthen the importance of [10] Murdoch IA, Turner C, Dalton RN. Arterial or mixed venous lactate our finding, that there is a real difference in the lactate levels measurement in critically ill children. Is there a difference? Acta measured at different sampling sites. Paediatr 1994;83:412-3. [11] Fauchere JC, Bauschatz AS, Arlettaz R, Zimmermann-Bar U, Bucher Laboratory testing includes collection and analysis of HU. Agreement between capillary and arterial lactate in the newborn. blood samples. Both the method and site of blood collection Acta Paediatr 2002;91:78-81. might contribute to analytical variability. In 1985, Neptun [12] Oliva P. Lactic . Am J Med 1970;48:209-21. et al [16] reported the effect of different blood collection [13] Waldau T, Larsen VH, Bonde J, Fogh-Andersen N. Lactate, pH, and procedures and sampling site selection on analysis of serum blood gas analysis in critically ill patients. Acta Anaesthesiol Scand Suppl 1995;107:267-71. chemistry parameters in rats. Their conclusion was that [14] Lavery RF, Livingston DH, Tortella BJ, Sambol JT, Slomovitz BM, sampling site and collection method may be a major source Siegel JH. The utility of venous lactate to triage injured patients in the of variation in clinical chemistry measurements, and might trauma center. J Am Coll Surg 2000;190:656-64. have an influence over the interpretation of treatment-related [15] Gallagher EJ, Rodriguez K, Touger M. Agreement between peripheral changes in individual parameters. venous and arterial lactate levels. Ann Emerg Med 1997;29:479-83. [16] Neptun DA, Smith CN, Irons RD. Effect of sampling site and In conclusion, our study demonstrated that blood lactate collection method on variations in baseline clinical pathology levels differed among the three sampling sites, and that it parameters in Fischer-344 rats. 1. Clinical chemistry. Fundam Appl was highest in the peripheral vein site. Toxicol 1985;5:1180-5.