| | Supplemental perioperative fluid administration increases tissue oxygen pressure☆☆☆★Accepted 15 August 2003. Abstract Background. Wound infections are common and serious surgical complications. Wound perfusion delivers oxygen, inflammatory cells, growth factors, and cytokines to injured tissues. Hypoperfused regions experience low oxygen tensions that do not support adequate oxidative killing or wound healing. Clinicians may fail to recognize clinically important hypovolemia because hemodynamic stability and urine output are maintained after peripheral perfusion is compromised. We tested the hypothesis that supplemental fluid administration during and after elective colon resection increases tissue perfusion and tissue oxygen pressure. Methods. Fifty-six patients undergoing colon resection were randomly assigned to conservative (8 mL·kg−1·h−1, n = 26) or aggressive (16 to 18 mL·kg−1·h−1, n = 30) fluid management. Anesthetic technique was standardized. We used 60% nitrous oxide in 40% oxygen. During surgery and postanesthetic recovery, subcutaneous oxygen tension (PsqO2) was measured by using a polarographic sensor implanted subcutaneously into 1 upper arm. Capillary blood flow was evaluated postoperatively with a thermal diffusion system. Data were analyzed with 2-tailed t tests; P value less than .05 was considered statistically significant. Results. Hemodynamic and renal responses were similar in the groups. Intraoperative tissue oxygen tension was significantly greater in patients given supplemental fluid: 81 ± 26 vs 67 ± 18 mm Hg, P = .03. Postoperative PsqO2 (77 ± 26 vs 59 ± 15 mm Hg, P = .009) and capillary blood flow (69 ± 12 vs 53 ± 12, P < .001) were also greater in the supplemental fluid patients. Conclusions. Supplemental perioperative fluid administration significantly increases tissue perfusion and tissue oxygen partial pressure. Optimizing tissue perfusion will require providing more fluid than indicated by normal clinical criteria or use of invasive monitoring to guide treatment. The actual effect of supplemental fluid administration on incidence of wound infection requires further investigation. (Surgery 2003;133:49-55.)
Wound infections are common and serious complications of surgery. Oxidative killing by neutrophils is the most important defense against pathogens causing surgical infections.1 Because oxygen is the substrate for oxidative killing, the rate of bacterial killing depends on tissue oxygenation over the entire physiologic range.2 It is therefore not surprising that the risk of surgical wound infection is inversely related to tissue oxygenation.3 In fact, Hopf et al4 suggest that measuring tissue oxygen as a factor in estimating wound vulnerability outperforms the entire Center for Disease Control index. Tissue oxygen is also an important substrate for tissue repair and wound healing by influencing prolyl and lysyl hydroxylases and consequently collagen synthesis.5
Various factors influence tissue oxygenation. For example, mild hypothermia triples the risk of infection by reducing tissue oxygenation; conversely, supplemental perioperative oxygen halves the risk of infection by increasing tissue oxygenation.6 However, even supplemental oxygen fails to improve oxygenation in hypoperfused tissues.3 Experimental wound hypoperfusion aggravates infections and reduces scar formation.7, 8, 9 It is thus evident that adequate perfusion is required for rapid healing and optimal resistance to infection.
Clinicians appreciate the need to maintain adequate perioperative vascular volume. However, adequate volume is usually defined by hemodynamic stability and good urine output because there is no routine clinical method for evaluating tissue perfusion. The difficulty with this approach is that hypovolemia critically reduces peripheral tissue perfusion long before compromising blood pressure, increasing heart rate, or reducing urine output.10, 11 Guided only by hemodynamic responses, clinicians may thus inadequately compensate for the enormous fluid losses associated with major surgery. Previous studies are consistent with this theory, demonstrating poor tissue oxygenation in many postoperative patients. We therefore tested the hypothesis that supplemental fluid administration during and after elective colon resection increases tissue perfusion and oxygenation.
Material and methods  After Institutional Review Board approval and informed consent, we studied 56 patients aged 18 to 80 years undergoing elective colon surgery. We excluded patients having recent fever or infection, Raynaud's syndrome, or any condition compromising peripheral perfusion such as smoking, diabetes, or peripheral vascular disease. Patients with a history of pulmonary edema and any form of renal failure were also specifically excluded from the protocol. Protocol Before surgery, patients were instructed in the use of a 100-mm visual analogue scale (VAS) to score their postoperative pain; 100 mm indicated the worse imaginable pain and 0 mm indicated no pain. All patients received standard mechanical bowel preparation with an electrolyte solution the night before surgery; they fasted for 8 hours before surgery. Intraluminal antibiotics were not used. Cefamandole (2 g) was given intravenously during induction of anesthesia, 6 hours postoperatively, and on the first postoperative day. Metronidazole (1500 mg) was administered during induction and the first postoperative day. Sodium thiopental (3 to 5 mg/kg), vecuronium (0.1 mg/kg), and fentanyl (1 to 3 μg/kg) were used for induction; anesthesia was subsequently maintained with isoflurane in nitrous oxide and oxygen (inspired fraction of oxygen [FiO2], 0.4) supplemented with fentanyl (1 μg·kg−1·h−1) or morphine (0.01 mg·kg−1·h−1). All patients were actively warmed intraoperatively with a forced air warmer (Bair Hugger; Augustine Medical, Eden Prairie, Minn) to maintain core temperature greater than 36°C. Patients were randomly assigned with computer-generated randomization numbers to conservative or aggressive fluid management. Those assigned to conservative fluid management were given a maintenance crystalloid infusion of 8 to 10 mL·kg−1·h−1 intraoperatively and for the first postoperative hour. This rate is the standard of care at Washington University. Patients assigned to aggressive fluid management were given a bolus of 10 mL/kg before induction of anesthesia. Subsequently, they were maintained with crystalloid infused at 16 to 18 mL·kg−1·h−1 intraoperatively and for the first postoperative hour. Blood loss in both groups was replaced with additional crystalloid in a 3:1 ratio. Plasma expanders (ie, hetastarch) were not given. However, additional fluid was given as necessary to maintain urine output of at least 1 mL·kg−1·h−1. Similarly, additional fluid was administered when mean arterial blood pressure decreased to less than 70% of preinduction values and was unresponsive to minor adjustments in the inhaled anesthetic concentrations. Target minimum hematocrit was determined on the basis of the patients' ages and cardiovascular status. The target hematocrit was 26% in patients aged younger than 65 years and 28% in patients aged 65 years or older having no significant cardiovascular diseases. Hematocrit was maintained at 30% or greater in patients with cardiovascular disease who were older than 65 years. Significant cardiovascular disease was defined as previous myocardial infarction, angina, congestive heart failure, cardiomyopathy, hypertension requiring treatment (or having a diastolic blood pressure exceeding 90 mm Hg), or peripheral vascular disease. Autologous and scavenged blood was administered at the discretion of the attending surgeon. Allogeneic blood was administered only as necessary to maintain the prospectively determined target hematocrits. This is the same strategy we have used in previous studies.12 Postoperative pain relief was maintained by patient-controlled analgesia with morphine (2-mg bolus, 6-minute lockout). Postoperative nausea and vomiting were treated, as necessary, with intravenous ondansetron (4 mg) by clinicians blinded to group assignment. During recovery, patients were given supplemental oxygen via nasal prongs at a rate of 2 L/min; additional oxygen was given as necessary to maintain arterial oxygen saturation at 95% or greater. Measurements Age, height, weight, gender, American Society of Anesthesiologists status, and preoperative laboratory values were recorded. We also recorded historical factors possibly influencing subcutaneous oxygen tension including smoking history and preoperative hemoglobin. Total fluid and opioids administered, urine output, and duration of surgery were recorded. We measured end-tidal isoflurane and carbon dioxide concentrations with an infrared detector at 15-minute intervals during anesthesia. Oxygen saturation was measured with a pulse oximeter throughout surgery, every 15 minutes in the postanesthesia recovery room, and once on each postoperative day. Core temperature in the distal esophagus was measured at 15-minute intervals during anesthesia. The lungs and heart sounds were auscultated at 15-minute intervals throughout surgery and every 30 minutes during the first hour of recovery. Subcutaneous oxygen tension (PsqO2) was evaluated with a polarographic tissue oxygen sensor (Licox, Inc, Kiel, Germany) positioned within a saline-filled polymeric silicone tube inserted into the subcutaneous tissue of the patients' upper arms after induction of anesthesia. (Polymeric silicone readily permits transfer of oxygen by diffusion.) The oxygen sensor is a flexible microcatheter probe used for long-term monitoring of the oxygen partial pressure (PO2) in tissue and body fluid. The PO2 sensor is an electrochemically reversible polarographic cell embedded into the tip of a completely sealed microcatheter tube. Temperature sensitivity of the sensor is 0.25%/°C, but a thermistor incorporated into the probe provides temperature compensation. The device was calibrated before anesthetic induction. Calibration remains stable (within 8% of baseline value for room air) in vivo for at least 8 hours.3, 13, 14 Oxygen sensors were calibrated in room air (ambient PO2, 154 mm Hg). For calibration purpose a calibration card was inserted into the Licox device. The calibration data of the connected Optode and other data are electronically stored on this card (factory calibration setting). All PsqO2 values measured before insertion were within 10% of 154 mm Hg. At the end of each study period, oxygen sensors were removed from the tonometers and allowed to equilibrate in room air. All PsqO2 values were within 10% of 154 mm Hg. The PsqO2 was measured at 15-minute intervals from 30 minutes to 180 minutes after induction of anesthesia during surgery and from 0 to 60 minutes postoperatively. Forearm minus fingertip, skin-surface temperature gradients (skin-temperature gradients) were measured on one arm and used as an index of arteriovenous shunt perfusion. This measure correlates well with fingertip volume plethysmography.15 Capillary blood flow (SBF) was evaluated with a capillary blood flow meter (THERMAL SBF-meter; MedTech, Ltd, Tel Aviv, Israel). The probe consists of a microheater that is coupled with an insulated thermistor that is positioned on the skin surface. The probe was positioned on the patient's upper arm adjacent to the subcutaneous oxygen tension probe. It has a diameter of approximately 5 mm and was placed at least 3 cm (6 diameters) lateral to the Licox probes to avoid increases in local blood flow by the heated probe. Blood flow was measured at 15-minute intervals throughout the 1-hour recovery period, as was pain. Data analysis All data except PsqO2 were first averaged within each patient for the intraoperative and postoperative periods. Values for each period were than averaged among the patients. They were subsequently analyzed with unpaired, 2-tailed t tests. Subcutaneous oxygen tensions during surgery were analyzed with repeated measures analysis of variance (ANOVA); Scheffé F test was used to compare intragroup means. Because postoperative subcutaneous oxygen tension values were not normally distributed, a natural log transformation was used in this repeated measures ANOVA. Results are presented as means ± standard deviations (SDs); P values less than .05 were considered statistically significant. Results Patient characteristics, surgery duration, and type of surgery were comparable in the groups (Table I).
| | |  | | Conservative fluid management | Aggressive fluid management | P value | |
|---|
| Number | 26 | 30 | | |
| Age (y) | 54 ± 12 | 53 ± 12 | .984 | |
| Weight (kg) | 73 ± 15 | 78 ± 19 | .253 | |
| Height (cm) | 169 ± 9 | 170 ± 10 | .936 | |
| Body mass index (kg/m) | 26 ± 6 | 26 ± 6 | .998 | |
| Gender (M/F) | 13/13 | 17/13 | .818 | |
| Hemoglobin (mg/dL) | 13.4 ± 1.8 | 13.2 ± 2.0 | .707 | |
| American Society of Anesthesiologists status (I/II/III) | 4/20/2 | 2/26/2 | .557 | |
| Type of surgery (colon/rectum) | 15/11 | 20/10 | .678 | |
| Duration of surgery (h) | 2.5 ± 1.1 | 2.5 ± 0.8 | .929 | |
| | | | | |
Intraoperative and postoperative hemodynamics, anesthetic management, postoperative pain management, oxygen administration, and core temperatures were similar as well (Tables II and III).
| | | | | Conservative fluid management | Aggressive fluid management | P value | |
|---|
| Mean arterial pressure (mm Hg) | 79 ± 8 | 79 ± 9 | .875 | |
| Heart rate (bpm) | 80 ± 16 | 82 ± 14 | .675 | |
| Core temperature (°C) | 36.0 ± 0.5 | 36.1 ± 0.5 | .231 | |
| Oxygen saturation in arterial blood (%) | 98 ± 1.1 | 99 ± 1.4 | .142 | |
| End-tidal isoflurane (%) | 0.9 ± 0.2 | 0.9 ± 0.3 | .946 | |
| End-tidal CO2 (mm Hg) | 32 ± 3 | 32 ± 3 | .358 | |
| Fentanyl (μg) | 161.5 ± 165.1 | 136.7 ± 103.3 | .496 | |
| Blood loss (mL) | 274 ± 338 | 249 ± 188 | .731 | |
| Fluid administered (mL) | 2173 ± 972 | 3815 ± 1853 | <.001 | |
| Urine output (mL/kg/h) | 2 ± 1 | 2 ± 2 | .258 | |
| | | | | |
| | | | | Conservative fluid management | Aggressive fluid management | P value | |
|---|
| Fluids (mL) | 649 ± 310 | 1183 ± 317 | <.001 | |
| Mean arterial pressure (mm Hg) | 92 ± 15 | 100 ± 16 | .059 | |
| Heart rate (bpm) | 75 ± 15 | 80 ± 14 | .185 | |
| Oxygen saturation in arterial blood (%) | 98 ± 2.0 | 98 ± 2.1 | .317 | |
| Skin-temperature gradient (°C) | 3.6 ± 2.8 | 1.6 ± 2.4 | .004 | |
| Skin blood flow | 53 ± 12 | 69 ± 12 | <.001 | |
| Morphine (mg) | 7.7 ± 5.8 | 10.5 ± 7.1 | .118 | |
| VAS (mm) | 29 ± 16 | 29 ± 21 | .918 | |
| | | | | |
Per protocol, the amount of intraoperative and postoperative crystalloid administered differed significantly in the 2 treatment groups. Furthermore, postoperative forearm-fingertip temperature gradients, a measure of arteriovenous shunt perfusion, were significantly greater in the conservative than in the aggressive fluid replacement group (3.6°C ± 2.8°C vs 1.6°C ± 2.4°C, P = .004). Postoperative SBF was also greater in the aggressive fluid management group (69 ± 12 vs 53 ± 12, P < .001) (Table III). Intraoperative tissue oxygen tension was significantly greater in patients given supplemental fluid: 81 ± 26 mm Hg vs 67 ± 18 mm Hg, P = .03. Postoperative PsqO2 was also significantly greater: 77 ± 26 mm Hg vs 59 ± 15 mm Hg, P = .009 (Fig 1).
Discussion Vascular volume is often inadequate in surgical patients.11 Hypovolemia begins with a conventional overnight fast, a deficit that may be incompletely replaced. Surgical tissue injury provokes blood loss and extravasation of intravascular fluids to interstitial spaces. Furthermore, large amounts of plasma are absorbed by drapes, and substantial fluid evaporates from within surgical incisions. Hypovolemia is especially likely in patients undergoing colon surgery because they undergo bowel preparation, usually with an electrolyte solution that produces copious diarrhea. Anesthesiologists naturally attempt to replace lost fluids, but they do so largely on the basis of clinical signs such as arterial blood pressure, heart rate, and urine output as well as calculations of deficit, maintenance, third space, and blood loss estimates. The difficulty with this approach is that hemodynamic responses and renal function are well preserved during mild or moderate hypovolemia. Consistent with this theory, hemodynamic responses were virtually identical in each of our treatment groups. Mean arterial pressure, for example, averaged 79 mm Hg in patients given both conservative and aggressive fluid replacement. Heart rate was also similar in the 2 groups, and urine output easily exceeded 1 ml·kg−1·h−1 in both groups. A key mechanism by which systemic responses are maintained during hypovolemia is restriction of peripheral blood flow to maintain perfusion of the brain and abdominal organs. As a consequence, peripheral tissues suffer disproportionate hypoperfusion during even mild hypovolemia. Peripheral tissue hypoperfusion is aggravated because the subcutaneous tissue and skin serve as volume reservoirs (about 20% in a euvolemic person) that supply the central compartment during hemorrhage or dehydration. Consequently, tissue oxygen tension, which is largely determined by tissue perfusion, is critically sensitive to sympathetically induced vasoconstriction. Hypovolemia,3 thermoregulatory vasoconstriction,16 epinephrine infusion,17 pain,18 and cigarette smoking19 have thus all been shown to decrease PsqO2 via this mechanism. Despite similar hemodynamic responses, subcutaneous oxygenation was significantly lower (67 ± 18 mm Hg) in our patients who were assigned to less fluid than in those who were generously hydrated (81 ± 26 mm Hg). Similar reductions are associated with highly clinically important increase in the risk of surgical wound infection.4 For example, smoking19 and core hypothermia similarly decrease tissue oxygenation ~15 mm Hg.16 Both these conditions have been shown to significantly increase the risk of wound infection.20 Larger increases in peripheral tissue oxygenation induced by supplemental oxygen reduce infection risk by a factor of 2.6 Our current results, combined with previous observations, thus suggest that mild hypovolemia is likely to produce a clinically important increase in the risk of surgical wound infection. Hypovolemic surgical patients presumably reestablish normal fluid balance after some days of recovery. However, the first few hours after bacterial contamination constitute a decisive period during which infection is established.7 For example, antibiotics limit infection when given within 2 hours of bacterial inoculation but are subsequently ineffective.21, 22 Some studies suggest a longer decisive period for oxygen.23 However, the major effect of inadequate tissue perfusion on wound healing and resistance to infection is likely to occur during the decisive period intraoperatively and in the initial postoperative hours. Consistent with this theory, interventions restricted to the perioperative period markedly influence the risk of infection. These interventions include maintaining normothermia,20 providing supplemental oxygen,6 and administration of a single dose of prophylactic antibiotics.24 Electrocautery artifact precluded using the THERMAL SBF-meter during surgery. We were, however, able to use the device postoperatively. The SBF-meter is an investigational device and has not been formally validated. Our data did not provide the necessary validation because we did not compare results from this thermal diffusion system with an established measure of cutaneous perfusion. Nonetheless, the SBF-meter suggests that peripheral tissue perfusion was reduced ~25% in the group given conservative amounts of fluid. This seems consistent with the observed ~25% reduction in postoperative tissue oxygen partial pressure. We evaluated subcutaneous oxygen partial pressure in the upper arm rather than within the surgical incision. The arm was chosen, as in our previous studies,6 because values can be obtained during surgery from this site, whereas measurements from the incision are obviously restricted to the postoperative period. Also, the choice of measurement in the arm allowed us to compare our data to the data already available in the literature. Measurement of subcutaneous oxygen tension in the upper arm predicts surgical wound infection, and this has been validated in a number of studies. Measurement of oxygen in the wound has not been evaluated in the same way. Values from the arm correlate well with tissue oxygen pressures in the chest, although they are about 10 mm Hg greater.25 The postoperative PsqO2 values in our study were slightly higher than often reported in the literature.6 Arterial PO2 values were available in approximately 30% of the patients and averaged at 115 ± 34 mm Hg, which is comparable to previous studies. However, arterial pCO2 values averaged at 45 ± 6 mm Hg in our current study. It has recently been shown that an increase in pCO2 from 30 to 45 mm Hg increases tissue oxygenation by approximately 15%.26 Also, pain, which has been shown to decrease PsqO2, was scored relatively low in our study.18 The relatively high pCO2 as well as the fact that the patients did not experience significant pain might be an explanation for the higher PsqO2 values. In summary, supplemental perioperative fluid administration significantly increases tissue perfusion and tissue oxygen partial pressure. Previous work indicates that improved tissue oxygenation enhances wound healing and reduces infection risk. Because hemodynamic and renal responses were similar in each group, optimizing tissue perfusion will require either providing larger amounts of fluid than indicated by normal clinical criteria or use of invasive monitoring to guide treatment. However, the actual effect of supplemental fluid administration on the incidence of wound infection needs to be evaluated. References 1.
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St Louis, Mo, and Louisville, Ky From the Department of Anesthesiology, Department of Surgery, Section of Colon and Rectal Surgery, Washington University, St Louis, Mo, and the OUTCOMES RESEARCHTM Institute and Department of Anesthesiology, University of Louisville, Louisville, Ky ☆ Supported by NIH Grant GM 58273, the Joseph Drown Foundation (Los Angeles, Calif), and the Commonwealth of Kentucky Research Challenge Trust Fund (Louisville, Ky). The THERMAL SBF-meter was donated by MedTech, Ltd (Tel Aviv, Israel). ☆☆ Reprint requests: Andrea Kurz, MD, Department of Anesthesiology, Washington University, 660 S Euclid Ave, St Louis, MO 63110. ★ 0039-6060/2003/$30.00 + 0 PII: S0039-6060(02)21602-5 doi:10.1067/msy.2003.80 © 2003 Published by Elsevier Inc. | |
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