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American Journal of Critical Care. 2002;11: 554-566

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Journal Club Feature

Effects of an Augmented Postoperative Fluid Protocol on Wound Healing in Cardiac Surgery Patients

By Stacy Heiner, RN, BSN, JoAnne D. Whitney, RN, PhD, Connie Wood, RN and LTC Brenda I. Mygrant, AN, USA (retired). From Nursing Research Service, Madigan Army Medical Center, Tacoma, Wash (SH, CW), Department of Biobehavioral Nursing and Health Systems, School of Nursing, University of Washington, Seattle, Wash (JDW), and Continuing Medical Education Department, Dannemiller Memorial Educational Foundation, San Antonio, Tex (BIM).


    Abstract
 Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 
Background Cardiac surgery patients are vulnerable to hypoperfusion postoperatively and often have subcutaneous tissue oxygen tension less than 50 mm Hg. Hypovolemia most likely contributes to this hypoperfusion and may lead to impaired wound healing.

Objective To determine if a modified postoperative fluid replacement protocol would result in improved tissue oxygen tension, blood flow, and healing in cardiothoracic surgery patients.

Methods A total of 166 cardiac surgery patients, 18 to 90 years old, participated in a randomized, 2-group, repeated-measures study. The experimental group received fluid augmentation during the first 36 hours after surgery; the control group received standard postoperative replacement fluids. Subcutaneous tissue oxygen tension and temperature were measured 8, 18, and 36 hours after surgery. Tissue cellularity and accumulation of hydroxyproline were evaluated in tissue obtained from subcutaneous expanded polytetrafluoroethylene tubes. Wound complications were evaluated by using the ASEPSIS Wound Scoring System.

Results Tissue oxygen levels, tissue cellularity, and accumulation of hydroxyproline were similar in the 2 groups. A negative correlation (P = .01) existed between higher tissue oxygen values and lower (better) ASEPSIS leg wound scores. More than 80% of the patients had tissue oxygen levels of 50 mm Hg or less at each time of measure. Many values were 30 to 40 mm Hg less than the ideal for control of bacteria and healing.

Conclusions The frequency of low oxygen levels is consistent with data from earlier studies. Determination of other interventions to improve subcutaneous tissue perfusion in cardiac surgery patients is needed.


Tissue wounding may result from surgery or accidental trauma. Delayed wound healing and wound infection prolong hospital stay, increase healthcare costs, and contribute to morbidity and mortality.1 Although many factors are important for wound healing, tissue blood flow and oxygen levels are among the most critical in promoting enhanced wound healing and resistance to wound infection.2–7 Therapies to improve wound perfusion and oxygenation and thus potentially improve wound healing outcomes have not been fully developed or tested. Methods that promote more efficient wound healing could increase cost-effective care.


    Background
 Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 
Because of the importance of perfusion and oxygen availability to successful wound healing, assessment and prevention of reductions in blood flow and tissue hypoxia, particularly in the skin and subcutaneous tissue, deserve attention. Blood flow to these tissues is often systemically sacrificed after injury to preserve vital organ perfusion, placing injured peripheral tissues at risk for complications.8 Increasing evidence indicates that hypovolemia is a common contributor to tissue hypoxia. Subcutaneous tissue oxygen tension (PscO2) decreases as circulating fluid volume decreases. Peripheral tissue perfusion may be depressed even when standard clinical parameters such as cardiac output, cardiac index, and/or urine output, which are routinely used to assess hydration, remain within acceptable limits.2,8–10

In studies in which PscO2 was used as an index, reductions in subcutaneous perfusion were detected in patients after surgery, even when parameters such as urine output and cardiac index remained adequate by accepted standards.2,10 More than one third of postoperative patients studied had hypoperfusion as indicated by PscO2. PscO2 was remarkably lower in patients who had cardiac or vascular procedures (25–50 mm Hg) than in patients who had abdominal surgery or mastectomy (46–69 mm Hg), placing those who had cardiac or vascular surgery at higher risk for wound complications and infection.2 PscO2 in cardiac surgery patients receiving a fraction of inspired oxygen (FIO2) as high as 0.80 was still less than the PscO2 in patients who had the most extensive abdominal surgery who were receiving 100% room air, but did improve with small volumes of supplemental fluids (eg, 250–500 mL). A fluid challenge as small as 50 mL can increase PscO2 for as long as 2 hours. 10

Hypovolemia, a common condition after cardiac surgery because of loss of blood and decreased diastolic filling, most likely contributes to diminished peripheral tissue oxygen and blood flow and, therefore, impaired healing. Concern about keeping the workload of the heart down may lead to decisions about fluid repletion that are weighted toward reduced blood volume, but reduced blood volume also tends to increase vulnerability to wound complications. The prevalence of sternal wound infections among adults is 0.5% to 5%, with a resulting morbidity of up to 80%.11–15

In one study16 of patients having abdominal surgery, healing was improved when decisions about fluid replacement were based on tissue oxygen measurements rather than blood pressure, heart rate, and urine output. Compared with the control group, patients who received additional fluids (mean increase, 1.1 L more than control group on the day of surgery) had both significantly higher PscO2 on the first postoperative day and higher amounts of hydroxyproline (a measure of collagen) in test wounds on the seventh postoperative day.

A logical extension of this research is to test the effects of postoperative hydration in other groups of patients. Studies on the effects of postoperative hydration are particularly important for cardiac surgery patients because of the high risk of these patients for tissue hypoxia and wound complications. The presence of a pulmonary artery central catheter also provides a means to monitor and measure cardiac indicators of hydration.

Relatively little is known about the amount of fluid required after surgery to maintain peripheral or regional perfusion and if, in specific groups of patients, supplemental fluids will maintain tissue oxygen at levels that promote healing. We did the study reported here to determine the effects of an augmented fluid replacement protocol after open heart surgery on PscO2, subcutaneous tissue perfusion, wound healing, and wound complications and to further explore the relationships between subcutaneous tissue oxygen levels and wound healing.


    Methods
 Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 
Computer-generated random numbers in blocks of 10 were used in a randomized, 2-group, repeated-measures design. The human subject review boards of the institutions involved approved the study. Informed written consent was obtained from each patient who agreed to participate, and each patient was randomly assigned to the control or the experimental (intervention) group by using blocked randomization.

Sample
Participants were recruited from patients, 18 to 90 years old, scheduled for coronary artery bypass graft surgery and/or cardiac valve repair/replacement. Patients were asked to participate if they were free from obvious impediments to healing, including long-term corticosteroid therapy, renal disease, and severe respiratory dysfunction. Patients with left ventricular ejection fraction less than 0.40 and/or those with Cleveland Clinic scores17 greater than 6 were not eligible for the study.

Descriptive Variables
Data on specific descriptive variables were collected to test for threats to internal validity and the effectiveness of randomization and to describe the generalizability of the sample. The descriptive variables were selected because of their potential confounding effect on the outcome measures. Specifically, variables that influence the oxygen, perfusion, or wound healing measures, or those for which a strong theoretical basis exists for influencing the outcome measures, were selected.

Results of research with animal models indicated that the rate of collagen synthesis is slower in older animals.18 Impairment of collagen synthesis is also associated with certain diseases (eg, diabetes, uremia).19,20 Smoking and increasing age reduce both tissue oxygen levels and perfusion score, and collagen deposition in subcutaneous test wounds was depressed in smokers.19,21 The prevalence of protein-calorie malnutrition among patients admitted to a hospital is 7.6% to 50%, depending on the preoperative diagnosis and the specific criteria used to establish nutritional status.17,22 Measures to assess protein stores indirectly, such as serum levels of prealbumin and transferrin, were included because the formation of collagen requires an adequate supply of protein (as well as vitamins and minerals), and nutritional depletion can adversely affect accumulation of hydroxyproline.23

Because severe anemia, defined as a hematocrit less than 0.15, significantly depresses PscO25 we determined, intraoperative estimated blood loss and obtained serial measurements of hematocrit. Derangement of the hemostasis system due to prolonged cardiopulmonary bypass may also contribute to a decreased hematocrit24; therefore, we recorded the duration of cardiopulmonary bypass. The time of surgery and time of PscO2 recording were noted to observe for effects of circadian rhythm.

Subcutaneous Oxygen Levels
A microcatheter oxygen sensor (miniature Clark electrode)/tonometer system and oxygen monitor (LICOX PO2 Computer, Medical Systems Corp, Greenvale, NY) were used to measure PscO2. The oxygen sensor is a high-precision oxygen-measurement probe. For each sensor, the sensitivity, the temperature coefficient of sensitivity, the zero current, the 12-hour stability, and the reaction time are determined individually during production. When standard calibration methods are used, the oxygen sensor has a sensitivity calibration error less than ±1% of true PO2 value and a zero calibration error of less than 1 mm Hg. The stability of the sensor allows up to 12 days of continuous oxygen measurement. The system includes a thermocouple to record subcutaneous temperature.

For the tissue measurements, a silastic tonometer was inserted subcutaneously in the dorsal part of the left upper arm, covered with a 7.7 x 12.7-cm (3 x 5-in) transparent dressing, and left in place; the oxygen sensor and thermocouple were introduced into the tonometer at the time of each oxygen measurement. The arm provides an accessible standardized wound where measurements can be taken in the same tissue location each time. The method is minimally invasive, is well accepted by patients, and has been used extensively in clinical studies.2,5,10,16,21,25,26 Oxygen tension measured in a standardized subcutaneous tonometer in a patient correlates with PscO2 in the surgical wound of the same patient, although it is approximately 6 to 10 mm Hg higher.25

Subcutaneous Perfusion Score
A perfusion score reflecting delivery of oxygen to subcutaneous tissue (based on the Fick principle and determined by using the PscO2 data) was calculated during each measurement.27

On the basis of studies in animals and humans,27 oxygen extraction in subcutaneous wounds when perfusion is normal is approximately 0.7 mL per 100 mL of blood. Under normal conditions, as PaO2 increases in response to breathing of supplemental oxygen, even to levels greater than full hemoglobin saturation, PscO2 also increases; the relationship is linear when PaO2 reaches 300 mm Hg.5 However, as blood flow decreases and oxygen extraction increases to more than 0.7 mL per 100 mL of blood, the extent to which PscO2 increases in response to supplemental oxygen diminishes. Hence, lack of a change in PscO2 in response to supplemental oxygen suggests increased oxygen extraction and poor perfusion.10 Study of the relationship between tissue oxygen and blood flow (with oxygen used as a relative and not an absolute indicator of blood flow) indicated that tissue oxygen and blood flow are significantly correlated (r=0.91, P<.01).5

In the study reported here, a perfusion score of 1 indicates a 20% or greater increase in tissue oxygen in response to breathing oxygen; a score of 0 indicates a lesser response. Interpretation of the score is based on the fact that elevations in PscO2 in response to increased FiO2 are possible only if the tissue oxygen extraction is small and perfusion is excellent.5 With this interpretation, the use of supplemental oxygen and the subsequent tissue oxygen response can be used as a relative measure of perfusion in subcutaneous wounds. The percent increase in PscO2 response to supplemental oxygen was calculated at the time of each PscO2 measurement.

Subcutaneous Test Wounds
Small test wounds were created in the subcutaneous tissue according to a method developed for the study of wound healing in humans.26 A 10-cm segment of expanded polytetrafluoroethylene (ePTFE) tubing (International Polymer Engineering, Tempe, Ariz) sutured to a 22-gauge Keith needle was inserted approximately 2 to 3 cm into the subcutaneous tissue in the dorsal aspect of each patient’s left arm until only 1 to 2 cm remained above the surface of the skin. The Keith needle was removed, a single silk suture was used to secure the remaining 1- to 2-cm "pigtail" to the patient’s skin, and a 7.7 x 12.7-cm transparent adhesive dressing was placed over the wound. The ePTFE tube and its contents were removed on the seventh postoperative day, providing a tissue sample for biochemical analysis.

The ePTFE tubing has a pore size of 90 to 120 µm, which allows migration and entry of cells, growth of new vessels, and deposition of connective tissue. The ePTFE tube technique has been tested in many studies on healing in animals and humans.2,5,16,21,26,28 By the fifth day after implantation, a significant increase in the amount of hydroxyproline in the contents of the tube occurs, which is followed by a consistent increase from day 5 to 7. Removal of the ePTFE tube at 7 days is standard in wound healing studies.5,29 The amount of hydroxyproline in the contents of the ePTFE tube is strongly correlated with surgical wound tensile strength (r = 0.75).29 The ePTFE tube is well tolerated by patients and is associated with minimal complications.5,16,21,26,28

Measurement of Hydroxyproline
The amount of hydroxyproline in tissue samples was determined by using high-performance liquid chromatography and the reagent 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole chloride.30 The method is sensitive enough that picomolar quantities of hydroxyproline can be detected, allowing the analysis of small quantities of tissue. Samples were analyzed in 1 of 2 assays to minimize interassay variation.

Histological Evaluation
A section of each ePTFE implant was examined histologically to evaluate the presence of inflammatory cells and fibroblasts and the character of the connective tissue formed within the implant. Cellular composition and formation of connective tissue were scored on a scale from 0 to 3. This scale is commonly used to describe cellular responses in tissue samples.18,20,31 It was used in this study to provide semiquantitative information on the intensity of cellular response, to evaluate any unusual cellular responses (eg, excessive neutrophil infiltration), and to supplement the data on hydroxyproline.

Histological examinations were done in 2 sets to decrease interrater variability. A pathology resident did the initial histological analysis. A subsequent recheck, by the same resident, of a random selection of 10% of the samples indicated a greater than 90% intrarater reliability. A staff pathologist also analyzed a random selection of 10% of the samples. Comparison of the resident’s and the staff pathologist’s results revealed a greater than 90% interrater reliability.

Wound Complications/Infection
The prevalence of wound complications and infection in the sternal wound and the wound at the access site for the donor vessel was determined by using the ASEPSIS scoring method, developed for use with cardiac surgery patients.22 Comparisons of ASEPSIS evaluations with standard definitions of wound infection or complications indicated that ASEPSIS is as sensitive as and significantly more specific than other indicators of wound problems.32

The surgical incision was evaluated for serous exudate, erythema, purulent exudate, and separation of deep tissues. The proportion of the wound, measured to the nearest 10% of the length of the wound for each characteristic, was assigned a numerical score of 0 to 30. Additional factors were assessed and scored, including additional treatment (antibiotics, drainage and/or debridement of the wound while the patient was anesthetized) and isolation of bacteria. Each wound was given a daily score for the first 5 days after surgery. The 5 scores combined indicated the severity of infection: 0 to 10, satisfactory healing; 11 to 20, disturbance of healing; 21 to 30, minor wound infection; 31 to 40, moderate wound infection; and greater than 40, severe wound infection.

Before data collection began, a greater than 90% interrater reliability for each subscore and the total score was ensured among the 3 members of the research team who were to do ASEPSIS scoring. A recheck of inter-rater reliability at the midpoint of the study indicated that the greater than 90% reliability was maintained.

Procedures
A member of the research team approached potential participants in the cardiothoracic clinic to explain the study and answer any questions. Informed consent was obtained. Serum levels of prealbumin and transferrin were determined for each participant at the time routine preoperative blood studies were done.

Each patient’s condition was reviewed after discharge from the operating room to ensure continued eligibility. Patients who were no longer eligible (because of prolonged cross-clamping or cardiopulmonary bypass or need for intra-aortic balloon pump therapy) were dropped from the study. Each eligible patient had a tonometer and an ePTFE tube placed by a member of the research team as previously described. The tonometer and ePTFE tube were placed parallel to each other, 2 to 3 cm apart, while the patient remained anesthetized.

Random assignment to the conventional or the augmented fluid replacement protocol was made approximately 8 hours after postoperative admission to the surgical intensive care unit. This time was chosen because retrospective chart reviews indicated that most cardiac surgery patients have achieved hemodynamic stability (ie, vital signs within normal limits, cessation of vasopressors and/or blood volume replacement) by the eighth postoperative hour. A Bair Hugger (Augustine Medical, Inc, Eden Prairie, Minn) chest blanket was placed on each patient upon arrival from the operating room and was used until the patient had a core temperature of at least 36.2°C (97°F).

The first PscO2 measurement was obtained 8 hours after surgery. Measurements were made with the subject supine with the head of the bed elevated 30°. Hypoxic isotonic sodium chloride solution was infused into the tonometer and allowed to equilibrate with the PO2 in the surrounding tissue for 20 to 30 minutes. Baseline descriptive data were also collected: oxygen saturation as measured by pulse oximetry, arterial oxygen saturation, mean arterial pressure, heart rate, respiratory rate, pulmonary artery pressure, cardiac index, systemic vascular resistance, core temperature, and subcutaneous temperature.

The oxygen sensor was introduced into the tonometer. The sensor provided a mean oxygen score for the local area of tissue in the arm. The baseline measurement was made with the subject breathing room air, or the percentage of oxygen required to maintain arterial saturation greater than 90%, until a stable PscO2 was reached. For this study, maximum, stable PscO2 was a PscO2 that varied by less than 2 mm Hg for at least 5 minutes. Measurement continued during an oxygen challenge. During the challenge, the subject breathed an increased concentration of oxygen (40% oxygen for those breathing room air and 20% greater than maintenance oxygen level for those already receiving supplemental oxygen). PscO2 was recorded again when a maximum, stable level was reached. If the PscO2 did not increase by 20% or more above baseline in response to the change in FIO2, a blood sample was obtained for arterial blood gas analysis to confirm adequate pulmonary function.

A fluid challenge was then given to those patients in the experimental group. PscO2 was monitored and recorded during and at the end of the fluid challenge. Once the PscO2 measurement was complete, FIO2 was returned to the settings used before the oxygen challenge, and PscO2 was monitored and recorded hourly during the next 12 hours. Additional measurements of PscO2 were obtained 18 and 36 hours after surgery by using the same procedure, including a fluid bolus if required as indicated by the PscO2. After the final measurement, the tonometer was removed.

A member of the research team removed the ePTFE tube on the seventh day after surgery. If a patient was discharged home before the seventh postoperative day, the tube was removed in the patient’s home. The implant was removed, and the 2.5-cm part of the implant that had been outside and immediately below the skin was discarded. A 1-cm piece of the tube was then removed from the center of the implant and placed in 10% formaldehyde for histological analysis. The remaining 2 parts were measured for length and weight and then stored at -70°C until analyzed for hydroxyproline content.

The sternal, access site for the donor vessel, and nonsurgical wounds were assessed daily for the first 5 days after surgery by using the ASEPSIS scale by 1 of the 3 members of the research team. Interrater reliability was achieved before the study started and was maintained throughout the study period as previously described.

Conventional Fluid Replacement
After their return to the coronary care unit from the operating room, patients in the control group received standard conventional postcardiac surgery intravenous fluids of 20 mL/h of isotonic sodium chloride solution via a pulmonary artery catheter until they were taking fluids by mouth (approximately 1 day). Blood components and any additional fluid were administered as ordered by the surgeon on the basis of hematologic laboratory findings, pulmonary artery diastolic pressure, and cardiac index.

Augmented Fluid Replacement
After their return to the coronary care unit from the operating room, patients in the experimental group received standard conventional postcardiac surgery intravenous fluids until they were taking fluids by mouth (approximately 1 day). Additional fluid augmentation was standardized to 3 tissue oxygen measurements as follows: For each of the PscO2 measurements (at 8, 18, and 36 hours after surgery), a baseline tissue oxygen level was established. The patients were then given an oxygen challenge as described previously. The challenge typically took 30 to 60 minutes. If PscO2 did not increase 20% or more above baseline with the oxygen challenge, 250 mL of isotonic sodium chloride solution was infused intravenously over 20 to 30 minutes. During administration of the fluid, PscO2 was recorded and the fluid was given until a maximum, stable PscO2 was reached. Additional isotonic sodium chloride solution was given at a rate of 40 mL/h for a period of 6 hours, beginning after completion of the initial (8 hour) postoperative PscO2 measurement. In total, patients in the experimental group may have received up to 990 mL of additional intravenous isotonic sodium chloride solution (a 250-mL bolus with each of the 3 PscO2 measurements plus an additional 240 mL given from 8 through 14 hours after surgery), depending on tissue oxygen levels. This administration of intravenous flu-ids was designed to support peripheral perfusion but not induce interstitial edema or other fluid-related complications.

During times of additional fluid administration (as described previously), a member of the research team monitored the patient’s pulmonary artery diastolic pressure. If the pressure increased to greater than 20 mm Hg at any time during the administration, the fluid infusion was stopped until the pressure decreased to less than 20 mm Hg and the infusion could be safely restarted. If the pressure remained greater than 20 mm Hg for more than 1 hour, the fluid challenge for that measurement point (8, 18, or 36 hours) was discontinued.


    Results
 Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 
Characteristics of the Sample
A total of 317 patients were eligible to participate during the study period; of these, 166 consented to be in the study. Seven patients were excluded from the study preoperatively because of a marked decline in physiological status. Twelve patients were dropped postoperatively because of surgical complications (extended intraoperative cross-clamp time >120 minutes and/or intraoperative cardiopulmonary bypass time >240 minutes), postoperative intra-aortic balloon pump therapy, research equipment or supply issues, or early discharge from the geographic area (>50 miles from study hospital). A total of 74 subjects in the control group and 75 in the experimental group completed the protocol. Tables 1Go and 2Go give the characteristics of the 2 study groups. Table 3Go gives baseline cardiac function for both groups at each PscO2 measurement.


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Table 1 Preoperative and postoperative descriptive variables

 

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Table 2 Frequencies by group and sex for selected descriptive variables*

 

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Table 3 Cardiac function at baseline 8, 18, and 36 hours after cardiac surgery

 
Subcutaneous Tissue Oxygen
The mean baseline PscO2 values 8, 18, and 36 hours after surgery for the 2 groups are given in Table 4Go. Repeated-measures analysis of variance (ANOVA) indicated that the daily maximum PscO2 decreased significantly over time (F = 4.9; P = .007); however, differences between the 2 groups were not significant.


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Table 4 Baseline subcutaneous tissue oxygen tension (mm Hg) 8, 18, and 36 hours after cardiac surgery*

 
For subjects in the experimental group who received the fluid bolus, the PscO2 before administration of the bolus was compared with the PscO2 after the administration (t test for paired samples). A fluid bolus was given to 37 patients 8 hours after surgery, to 3 patients 18 hours after surgery, and to 22 patients 36 hours after surgery. The additional fluid in these subjects did not increase PscO2 significantly.

Subcutaneous Tissue Perfusion
Patients with a perfusion score of 1 are referred to as "responders" and were considered well perfused. Frequencies of perfusion scores on each day of tissue oxygen measurements were compared between study groups by using the {chi}2 test. We found no significant differences in frequencies between the 2 groups. The number of responders in both groups increased daily. At 8 hours after surgery, 33% of all subjects were scored as responders. The percentage of responders increased to 47% at 18 hours after surgery and 62% at 36 hours after surgery.

Subcutaneous Temperature
Data on subcutaneous temperature were examined to determine if differences occurred between the 2 groups in the number of subjects who had low, normal, or high subcutaneous temperatures (<35°C, 35°C–36°C, and >36°C, respectively). No significant differences were detected (see FigureGo).



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Percentage of subjects with low (L, ≤35°C), normal (N, 35°C–36°C), and high (H, >36°C) subcutaneous temperatures 8, 18, and 36 hours after surgery.

 
Wound Healing
  Histology.   Tissue samples were evaluated by using a 0 to 3 semiquantitative scale. Mean scores are given in Table 5Go. Cellularity and character of the connective tissue were included in the evaluation. Samples were examined specifically for presence of polymorphonuclear leukocytes, macrophages, fibroblasts, loosely organized connective tissue, and organized connective tissue. Although the histological scores tended to be slightly higher in the experimental group than in the control group, no significant differences in mean rank were indicated by Mann-Whitney U analysis. The scores in both groups were low and indicative of a modest cellular response.


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Table 5 Mean histological scores of wound tissue 7 days after cardiac surgery*

 
  Hydroxyproline Content.   The mean hydroxyproline content in ePTFE samples was 0.1891 µg/mm for the control group and 0.1812 µg/mm for the experimental group. Differences between the 2 groups were not significant (t = 0.493, P = .62).

  Wound Infection/Complications.   The total ASEPSIS scores did not differ between the 2 groups for chest wounds or leg wounds ({chi}2=1.0, P=.50; {chi}2=1.8, P=.50, respectively).

Relationships Between Tissue Oxygen and Wound Healing Indicators
Spearman rank correlation coefficients were calculated between a subcutaneous oxygen score (3-day mean of the maximum PscO2 values obtained 8, 18, and 36 hours after surgery) and histological and ASEPSIS variables to explore relationships between tissue oxygen and wound healing. We found significant correlations between (1) PscO2 and the ASEPSIS score for the leg wound associated with graft harvest for the bypass procedure ({rho}s = –0.24; P = .01) and (2) PscO2 and the score for organized connective tissue in the ePTFE implants ({rho}s = –0.21; P = .01).

A Pearson correlation coefficient was calculated to explore the relationship between tissue oxygen (3-day mean of the maximum PscO2 values) and hydroxyproline content of the ePTFE implants. The relationship was not significantly correlated (r = 0.09, P = .30).

Fluid Intake
Repeated-measures ANOVA was used to compare the mean amount of crystalloid fluids, colloid infusions, and total fluid intake (all intravenous and oral fluids) for each day of the study. The experimental group received significantly more crystalloid fluids overall (F = 5.72; P = .01), and crystalloid infusion in both groups decreased significantly during the 3 days (F = 1284.7; P < .001). The experimental group received a mean of 170 mL more crystalloid fluids than did the control group on day 1 (the day of the surgery), a mean of 261 mL more on day 2, and mean of 154 mL on day 3.

We found no differences between the 2 groups for colloid infusions. However, colloid infusion levels decreased significantly over time for all subjects (F = 256.2; P < .001). Overall, total intake did not differ significantly between the 2 groups (F = 0.877; P = .35). The decrease in total intake over time was significant for both groups (F = 737.2; P < .001). Table 6Go gives the mean amount of fluid intake for each group on each day of the study.


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Table 6 Fluid intake and output after cardiac surgery*

 
Total Fluid Output
Repeated-measures ANOVA was used to compare mean amount of total fluid output between the 2 groups for each day of the study. We found no significant difference overall between the groups (F = 0.21; P = .64). The decrease in total output over time was significant for both groups (F=159; P<.01).

Medications
Medications given during a measurement or within 30 minutes before a measurement that might have affected tissue oxygen levels were recorded. The medications included nitroglycerin, norepinephrine, nitroprusside sodium, epinephrine, and furosemide. The frequencies of the medications were compared between the 2 groups for each of the measurement times. A {chi}2 analysis indicated in no significant differences between the groups related to medications given at the time of PscO2 measurement except for the drug furosemide.

At the time of the third oxygen measurement (36 hours after surgery), 20 patients in the experimental groups and 6 patients in the control group received furosemide. This difference was significant ({chi}2 = 9.0; P = .002). At the time of the second measurement (18 hours after surgery), 18 subjects in the experimental group and 9 in the control group received furosemide. This difference was not significant ({chi}2 = 3.5; P = .06). On the day of surgery, 18 subjects in the experimental group and 9 in the control group received furosemide within 30 minutes of the PscO2 measurement. This difference was not significant (P = .06).


    Discussion
 Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 
Significant differences in tissue oxygen levels were not evident between the 2 groups of patients. Although the experimental group did receive significantly more crystalloid fluids than did the control group, the mean difference in these fluids for the 3 days of the study was small (261 mL or less). Mean total intake of fluid did not differ between groups, a finding that may explain the similarity in tissue oxygen values for the 2 groups. Both groups received similar amounts of colloidal fluids and blood products. In previous studies,2,10 fluid infusions of 250 mL induced significant increases in PscO2 at the time of infusion, and the increases persisted for several hours after infusion. These findings were not confirmed by our results.

The mean PscO2 values (34–43 mm Hg) in both groups are similar to those reported by others who studied tissue oxygen levels in patients after cardiac surgery.2,33 In general, our values were less than the tissue oxygen levels in patients who had different types of surgery, for example, general abdominal procedures for which PscO2 levels of 65 to 76 mm Hg during oxygen supplementation are reported.16 The mean values in our study are also less than levels thought to be optimum for the prevention of healing complications such as infection.4

We explored other possible explanations for the low PscO2 levels we found. Cardiac index was within normal range for patients in both groups. Another possibility for low PscO2 is a low PaO2. When subjects did not respond to the oxygen challenge, a blood sample was obtained for arterial blood gas analysis if arterial access was available. After surgery, PaO2 was less than 95 mm Hg for 13% of patients in the control group and 12% in the experimental group at 8 hours; for 10% and 5% respectively, at 18 hours; and for 2% and 4%, respectively, at 36 hours. Thus, groups were similar, but these percentages indicate that in some subjects the lack of increase in PscO2 may have been related to low PaO2.

Data on perfusion scores are consistent with the data on tissue oxygen. The lack of differences is not surprising because of the relationship between tissue oxygen and the perfusion score. On the basis of the repeated-measures ANOVA, the increase in the numbers of subjects with positive perfusion scores for each day indicates a general improvement in peripheral perfusion as a function of time after surgery, for all subjects.

Patients in both groups had similar mean values for the amount of hydroxyproline in the ePTFE implant. This finding indicates that the supplemental fluid intervention did not affect the production of collagen in the patients in the experimental group. The hydroxyproline results are not surprising, because we did not detect an increase in tissue oxygen. Others16 found that abdominal surgery patients who had higher tissue oxygen levels because of increased amounts of crystalloid fluids had significantly higher levels of collagen in ePTFE implants.16 Had we been able to titrate fluid infusions to PscO2 levels, we might have had similar results. However, because of the legitimate concerns related to hemodynamic balance in patients who have cardiothoracic surgery, this approach was not possible. We cannot conclude that supplemental fluid as operationalized in our study is beneficial to healing.

The histological scores of both groups also did not differ significantly. The slightly higher scores in the experimental group are only suggestive of slightly greater infiltration of macrophages and fibroblasts and presence of loosely organized connective tissue. The scores in both groups were low and indicated only modest cellular infiltration. We are not aware of other studies on cellular infiltration in ePTFE implants, so we do not know how representative our data are. At this point, we can make no conclusions about the benefit of supplemental fluid in wound healing on the basis of this measure.

In contrast to the findings of other researchers, maximum tissue oxygen levels were not correlated to hydroxyproline accumulation in our samples. This difference may be due to the fact that the range of tissue oxygen scores we measured was small. As a whole, both groups of patients had relatively low scores; only a few subjects had higher maximum tissue oxygen scores (eg, 80 mm Hg and greater).

The negative correlations we found indicate that higher tissue oxygen was significantly related to lower (better) ASEPSIS scores for leg wounds and lower scores for the presence of organized connective tissue, meaning less extent of mature connective tissue. The correlation of ASEPSIS and the leg wound scores is in the expected direction and supports the importance of oxygen in limiting wound complications. The negative correlation of PscO2 and histological score for presence of organized connective tissue is not in the expected direction. The strength of both correlation coefficients are low, and therefore these results are viewed conservatively.


    Other Findings
 Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 
Furosemide
A factor that may have reduced the ability to detect any tissue effect of the supplemental fluid is the increased rate of furosemide administration close to the time of measurement in the experimental group. We recognized this trend during the study and met with the cardiac surgeons to discuss whether this increased rate was related to their knowledge of the study group to which the subject was assigned. Although information on each subject’s group assignment was readily available to them, all 3 cardiac surgeons stated that they paid no attention to group assignment when ordering furosemide. Rather, ordering of furosemide was based on a patient’s intake and output, change in weight from day to day, and laboratory values. On the basis of this information and the data indicating significant differences in furosemide administration between the groups, any effect of the intervention may have been attenuated by prescription of furosemide. The time of furosemide administration in relation to PscO2 measurements was considered coincidental.

Subcutaneous Temperatures
Mean subcutaneous temperatures for the groups at each of the PscO2 measurement times were within the following ranges: 8 hours after surgery, 30.1°C to 39.7°C; 18 hours after surgery, 30.7°C to 39.6°C; and 36 hours after surgery, 29.3°C to 39.4°C. Approximately one third of the subjects in each group had subcutaneous temperatures less than 35°C at any given measurement time. In this subset of subjects, core or tympanic temperatures were at least 37.0°C in 51% at 8 hours after surgery, 42% at 18 hours, and 49% at 36 hours. All subjects had core temperatures of 36.2°C before PscO2 was measured for the first time and use of the Bair Hugger chest blanket was discontinued. Because tissue response to breathing oxygen depends in large part on an open vascular bed and can be hindered during peripheral hypothermia, the relatively low mean PscO2 values and perfusion scores in both groups may be due in part to the number of subjects whose peripheral temperature was lower than normal.33,34


    Limitations
 Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 
The generalizability of our findings is limited because the study was done at a single institution. In addition, the sample consisted of fairly young and relatively healthy patients. Although this criterion for eligibility was selected to reduce factors that might confound results, it also reduces generalizability.

We attempted to establish normothermia by using active warming during the first 8 hours after surgery and before the first oxygen measurement. Because approximately 30% of patients in the sample had low subcutaneous oxygen levels at the time of each measurement, warming subjects for a longer period to increase the initial target temperature for normothermia or reinstituting active warming if needed may be important.

Oxygen measurements were obtained at 3 predetermined times. Obtaining the measurements is time and resource intensive, and others4,5,10,16,21,33 followed similar protocols with daily data collection points after surgery. We acknowledge that additional measurements could provide useful data on physiological responses to the intervention and a more complete perspective of changes over time.

We collected data on several medications that might influence outcome variables; however, we do not have detailed or complete information on pain medications or level of perceived pain. Poorly controlled pain might partly explain low PscO2, but we are unable to explore this variable as a potential factor.

The 2 groups had significant differences in 3 descriptive variables: duration of cardiopulmonary bypass (P = .03), duration of cross-clamping (P = .02), and serum levels of prealbumin (P = .007). In general, compared with patients in the experimental group, patients in the control group had somewhat longer bypass (15 minutes) and cross-clamp (14 minutes) times and lower prealbumin levels (209 vs 238 mg/L). Longer times in the operating room have been associated with lower PscO2 levels and may have affected tissue oxygen or collagen deposition in the patients in the control group. However, tissue oxygen and collagen deposition did not differ significantly between the 2 groups. The absolute differences were relatively small, and we did not interpret them as clinically significant.


    Conclusion
 Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 
The augmented fluid intervention we tested was based on literature suggesting that small increments in intravenously administered supplemental fluids most likely would increase PscO2 and benefit healing in cardiac surgery patients. Compared with patients in the control group, patients in the experimental group received an additional 154 to 261 mL of fluids, consistent with recommendations of earlier studies. This level of supplementation did not improve tissue oxygen or hydroxyproline levels. Most of the patients (both control and experimental) had PscO2 less than optimal both for collagen synthesis and bacterial clearance (≤50 mm Hg), and many had PscO2 of 30 to 40 mm Hg.3,4,16 Our results indicate a need to further explore the dose-response curve for fluid supplementation levels that are effective and safe in supporting tissue oxygenation.

Because of the delicate balance between fluid intake and hemodynamic stability in cardiac surgery patients, interventions other than, or in combination with, fluid supplementation may be more effective in maintaining peripheral perfusion levels that support wound healing. Establishing and maintaining normothermia in the early postoperative period (first 24–36 hours) is an intervention in need of testing that may be beneficial.


    ACKNOWLEDGMENTS
 
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in 45 CFR 46.

This research was sponsored by the TriService Nursing Research Program and was supported by 2 grants (TSNRP 94-0251A1, MDA 905-94-Z-0082 and TSNRP 95-051, MDA 905-95-Z-0024) totaling $739 280. The information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any official endorsement be inferred by, the Uniformed Services University of the Health Sciences, the Department of Defense, or the US Government.

The research was done at Madigan Army Medical Center, Tacoma, Wash.

To purchase reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints{at}aacn.org.


    REFERENCES
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 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 

  1. Ablaza V, Fisher J. Telemedicine and wound care management. Home Care Provid. 1998;3:206–211.[Medline]
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  27. Gottrup F, Firmin R, Rabkin J, Halliday BJ, Hunt TK. Directly measured tissue oxygen tension and arterial oxygen tension assess tissue perfusion. Crit Care Med. 1987;15:1030–1036.[Medline]
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  29. Byl NN, McKenzie AL, West JM, et al. Low-dose ultrasound effects on wound healing: a controlled study with Yucatan pigs. Arch Phys Med Rehabil. 1992;73:656–664.[Medline]
  30. Lindblad WJ, Diegelmann RF. Quantitation of hydroxyproline isomers in acid hydrolysates by high-performance liquid chromatography. Anal Biochem. 1984;138:390–395.[Medline]
  31. Pierce GF, Mustoe TA, Senior RM, et al. In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins. J Exp Med. 1988;167:974–987.[Abstract/Free Full Text]
  32. Wilson AP, Weavill C, Burridge J, Kelsey MC. The use of the wound scoring method "ASEPSIS" in postoperative wound surveillance. J Hosp Infect. 1990;16:297–309.[Medline]
  33. Kuttila K. Response of tissue oxygenation to systemic hyperoxia after surgery. Crit Care Med. 1990;18:369–372.[Medline]
  34. Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med. 1996;334:1209–1215.[Abstract/Free Full Text]

 

Journal Club Article Discussion Points

In a journal club, research articles are reviewed and critiqued. General and specific questions help to aid journal club participants in probing the quality of the research study, the appropriateness of the study design and methods, the validity of the conclusions, and the implications for practice.

When critically appraising the AJCC journal club article that you have just read, consider the questions and discussion points listed below.

  1. Description of the Study
  2. Literature Evaluation
  3. Sample
  4. Methods and Design
  5. Results
  6. Clinical Significance


These journal club discussion points can also be found online at www.ajcconline.org. Click on Journal Club. Also included on the Web site are "Guidelines for Critiquing Research," a helpful list of common questions used to guide a research critique, and "Glossary of Research Terms," a list of commonly used terms and their definitions. "Guidelines for Critiquing Research" and "Glossary of Research Terms" can also be accessed through AACN Fax on Demand by calling 800-222-6329; ask for item #4200 and item #4201, respectively.

 


    REFERENCE 
 Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Other Findings
 Limitations
 Conclusion
 References
 REFERENCE 
 

    Polit DF, Hungler BP. Nursing Research: Principles & Methods. Philadelphia, Pa: Lippincott; 1999.




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