Microcirculatory effects of intravenous fluid administration in anesthetized dogs undergoing elective ovariohysterectomy

Deborah C. Silverstein Department of Clinical Studies, Matthew J. Ryan Veterinary Hospital, University of Pennsylvania, Philadelphia, PA 19104.

Search for other papers by Deborah C. Silverstein in
Current site
Google Scholar
PubMed
Close
 DVM
,
Elizabeth M. Cozzi Abbott Animal Health, Abbott Park, IL 60064.

Search for other papers by Elizabeth M. Cozzi in
Current site
Google Scholar
PubMed
Close
 PhD
,
Amber S. Hopkins Department of Clinical Studies, Matthew J. Ryan Veterinary Hospital, University of Pennsylvania, Philadelphia, PA 19104.

Search for other papers by Amber S. Hopkins in
Current site
Google Scholar
PubMed
Close
 DVM
, and
Thomas J. Keefe EnviroStat Associates, 1524 Folsum Dr, Windsor, Colorado 80550.
Department of Environmental & Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Search for other papers by Thomas J. Keefe in
Current site
Google Scholar
PubMed
Close
 PhD

Abstract

Objective—To assess the microcirculatory effects of IV fluid administration in healthy anesthetized dogs undergoing elective ovariohysterectomy.

Animals—49 client-owned dogs.

Procedures—Dogs were sedated, and anesthesia was induced with propofol and diazepam and maintained with isoflurane in oxygen. Dogs received lactated Ringer's solution (LRS) IV at rates of 0, 10, or 20 mL/kg/h. Videomicroscopy was used to assess and record effects of LRS administration on microcirculation in the buccal mucosa. Measurements of microcirculatory (total vessel density, proportion of perfused vessels, microcirculatory flow index, and perfused vessel density by vessel size [< 20 μm, ≥ 20 μm, and all diameters]) and other physiologic variables (heart rate, Doppler-measured blood pressure, oxygen saturation as measured by pulse oximetry, capillary refill time, and body temperature) were compared among groups at baseline (immediately after anesthetic induction), 30 and 60 minutes afterward, and overall.

Results—Neither the proportion of perfused vessels nor microcirculatory flow index varied among treatment groups at any time point, regardless of vessel size. For vessels < 20 μm in diameter and for all vessels combined, total and perfused vessel density were similar among groups. For vessels ≥ 20 μm in diameter, total vessel density was significantly greater in the 20 mL/kg/h group than in other groups, and perfused vessel density was significantly greater in the 20 mL/kg/h group than in the 0 mL/kg/h group, when all time points were considered. Other physiologic variables were similar among groups.

Conclusions and Clinical Relevance—Total and perfused vessel density of vessels ≥ 20 μm in diameter (mostly venules) were greatest in dogs that received 20 mL of LRS/kg/h. Further research is required to evaluate clinical importance of these findings.

Abstract

Objective—To assess the microcirculatory effects of IV fluid administration in healthy anesthetized dogs undergoing elective ovariohysterectomy.

Animals—49 client-owned dogs.

Procedures—Dogs were sedated, and anesthesia was induced with propofol and diazepam and maintained with isoflurane in oxygen. Dogs received lactated Ringer's solution (LRS) IV at rates of 0, 10, or 20 mL/kg/h. Videomicroscopy was used to assess and record effects of LRS administration on microcirculation in the buccal mucosa. Measurements of microcirculatory (total vessel density, proportion of perfused vessels, microcirculatory flow index, and perfused vessel density by vessel size [< 20 μm, ≥ 20 μm, and all diameters]) and other physiologic variables (heart rate, Doppler-measured blood pressure, oxygen saturation as measured by pulse oximetry, capillary refill time, and body temperature) were compared among groups at baseline (immediately after anesthetic induction), 30 and 60 minutes afterward, and overall.

Results—Neither the proportion of perfused vessels nor microcirculatory flow index varied among treatment groups at any time point, regardless of vessel size. For vessels < 20 μm in diameter and for all vessels combined, total and perfused vessel density were similar among groups. For vessels ≥ 20 μm in diameter, total vessel density was significantly greater in the 20 mL/kg/h group than in other groups, and perfused vessel density was significantly greater in the 20 mL/kg/h group than in the 0 mL/kg/h group, when all time points were considered. Other physiologic variables were similar among groups.

Conclusions and Clinical Relevance—Total and perfused vessel density of vessels ≥ 20 μm in diameter (mostly venules) were greatest in dogs that received 20 mL of LRS/kg/h. Further research is required to evaluate clinical importance of these findings.

It is well known that anesthetized animals have increased fluid requirements as a result of vasodilation, decreased cardiac contractility associated with anesthetic agents, respiratory fluid losses while intubated, or a combination of these variables. Perioperative fluid administration is therefore recommended as a standard of care by the American Animal Hospital Association and American Association of Feline Practitioners for patients undergoing anesthesia.1 However, the use of IV fluid therapy during general anesthesia is not a universal practice in the care of small animal patients, and the deleterious effects of withholding fluids can be difficult to objectively quantitate. The IV administration of crystalloid fluids during anesthesia and surgery was studied as early as 1960, and documentation of acute reductions in extracellular fluid stores during major surgery in humans was reported the following year.2,3 Fluid administration in humans during general anesthesia has been associated with fewer occurrences of operative and postoperative hypotension, more rapid return of mentation and organ function, and faster elimination of administered drugs attributable to hepatic and renal metabolism and excretion, compared with results for patients who did not receive fluid treatment.4,5 Inadequate fluid treatment and decreases in tissue perfusion or oxygenation may also increase the risk of acute respiratory distress in humans undergoing surgery for treatment of oncological disease.6 In a small study7 of human patients with blood loss > 300 mL during intestinal resection, investigators found that IV administration of crystalloid fluids at rates of 10 to 15 mL/kg/h was sufficient to maintain cardiovascular stability and urine production, whereas delivery of fluids at a rate of 5 to 10 mL/kg/h was not. In another study, human patients undergoing colonic resection had higher subcutaneous tissue oxygen tension, capillary blood flow, and blood pressure when given IV fluids at 16 to 18 mL/kg/h during surgery rather than 8 mL/kg/h.8

The guidelines for the administration of IV fluids to dogs and cats during anesthesia have not been widely investigated, although hypotension was found to be the most frequently encountered anesthetic complication in the literature.9–11 Several fluid types have been recommended for the prevention of hypotension in anesthetized dogs, despite little evidence to support these guidelines.12–15 The potential adverse effects associated with perioperatively administered IV fluids must be weighed against the possible benefits in dogs.12 Adverse effects reported in humans include volume overload and subsequent pulmonary edema as well as cardiac and gastrointestinal dysfunction leading to postoperative complications and prolonged recovery times.16–18 However, no adverse pulmonary effects were observed in anesthetized cats and dogs that received LRS at 90 mL/kg/h for 60 minutes.19,20 In addition, it was recently reported that IV isotonic fluid delivery rates up to 30 mL/kg/h did not alter heart rate, arterial blood pressure, or urine production in healthy, anesthetized dogs, but cardiac output and pulmonary artery pressure increased following fluid administration of 20 or 30 mL/kg/h.21 These global measures of tissue perfusion are important to quantify oxygen delivery to the body, but microcirculatory vessels, comprising arterioles, venules, and capillaries within tissue beds, are ultimately responsible for delivering oxygen to the tissues and cells. Owing to their small sizes (< 100 μm in diameter), blood flow through these vessels is difficult to measure or quantitate without more advanced technology. To our knowledge, the effects of isotonic crystalloid fluid administration on the microcirculation in anesthetized animals have not previously been studied.

The purpose of the study reported here was to assess the effects of IV fluid administration on microcirculatory blood flow to the oral mucosa in healthy anesthetized dogs undergoing elective ovariohysterectomy. We hypothesized that dogs receiving an IV infusion of LRS would have significantly greater tissue perfusion than dogs that did not receive this treatment, as determined by assessment of microcirculatory variables of the buccal mucosa.

Materials and Methods

Animals—Forty-nine healthy, client-owned dogs undergoing elective ovariohysterectomy were enrolled in the study. All dogs were determined to be healthy on the basis of an unremarkable clinical history and results of a physical examination, CBC, and serum creatinine concentration. The study was approved by Institutional Animal Care and Use Committee of the University of Pennsylvania. Owner consent was obtained for all animals prior to study enrollment.

Anesthesia and instrumentation—A standardized premedication protocol consisting of hydromorphone hydrochloride (0.2 mg/kg, IM) and acepromazine maleate (0.01 mg/kg, IM) was used for all dogs. A 20- or 22-gauge IV catheter was placed aseptically in a cephalic vein. Anesthesia was induced with propofol (2 to 4 mg/kg, IV) and diazepam (0.25 mg/kg, IV) 30 to 45 minutes after premedication, and an orotracheal tube was placed.

A universal rebreathing circuita was used, and anesthesia was maintained with isoflurane delivered via an out-of-circuit isoflurane vaporizer with an end-tidal isoflurane concentration of 1.3% to 1.5% in oxygen. Adequate anesthetic depth was evaluated with standard clinical variables (ie, ventromedial rotation of the eyes, no palpebral reflex, no movement upon surgical stimulation). Mechanical ventilation was applied at 8 to 12 breaths/min to maintain Petco2 between 35 and 45 mm Hg and peak inspiratory pressure ≤ 20 cm H2O. A warm air blanket or heating pad was used to support body temperature.

Instrumentation for continuous monitoring of selected cardiorespiratory variables was established immediately after anesthetic induction. Three ECG leads were placed (2 at the elbow joints and 1 on a left pelvic limb) and the lead II ECG was continuously monitored to record heart rate and rhythm. An inflatable cuff with a diameter closest to 40% of the circumference of the antebrachium was placed on a forelimb proximal to the carpus, and the cuff was connected to a sphygmomanometer. Blood pressure was measured by use of a Doppler flow detector with a 9.5-MHz probe. With the use of acoustic coupling gel, the Doppler flow detector was placed on a clipped area over the common digital artery. Once a clearly audible signal was detected, the cuff was inflated to approximately 20 mm Hg greater than the point at which the Doppler signal was no longer audible. The cuff was slowly deflated, and the pressure at which a signal could again be detected was recorded. The cuff and Doppler probe were maintained within 3 cm of the level of the heart (ie, zero point). Tissue oxygen saturation was monitored by means of a pulse oximeter placed on the animal's tongue, and Petco2 was measured via sidestream sampling. A digital oral thermometer was placed sublingually to monitor body temperature.

Mucous membrane color and CRT were recorded. Following induction of anesthesia, dogs with observed cardiovascular or respiratory abnormalities (Doppler-measured blood pressure < 100 mm Hg, heart rate > 160 or < 60 beats/min, cardiac arrhythmias other than a sinus arrhythmia, or Spo2 < 95%), heavily pigmented oral mucosa at the mucogingival junction bilaterally, or a CRT > 2 seconds were removed from the study. If the patient's blood pressure decreased to < 90 mm Hg after inclusion in the study, a bolus of LRSb (15 mL/kg) was administered IV over 20 minutes. Heart rate, blood pressure, Spo2, and CRT were measured immediately after anesthetic induction and endotracheal intubation (ie, baseline) and at 30 and 60 minutes after induction. Body temperature was monitored throughout anesthesia; in 4 dogs/group, temperature was recorded at the same time points as other physiologic variables. Measurements were performed by 2 individuals, including one of the authors (DCS).

A videomicroscopec was used for evaluation of microcirculation in the buccal mucosa of all dogs. Microvasculature of the buccal mucosa was observed and recorded by 2 experienced investigators (DCS and ML) at baseline and at 30 and 60 minutes after anesthetic induction. After gentle removal of saliva from the mucogingival junction dorsal to a maxillary canine tooth with an isotonic saline (0.9% NaCl) solution–drenched gauze sponge, the microvascular network of the mucosa dorsal to the canine tooth was assessed via videomicroscopy with a 5× objective lens providing an on-screen 326× magnification. The probe tip was applied without pressure lateral and parallel to the canine tooth with the tip at the mucogingival junction. Three sequences of ≥ 20 seconds, each from different adjacent areas, were recorded at each time point with a computer and hard drive. Data were stored on an external hard drive for further analysis.

Fluid administration and surgery—Following induction of anesthesia, dogs were randomly assigned (by means of random number generator) to 3 IV fluid treatment groups (none [0 mL/kg/h], LRS at 10 mL/kg/h, or LRS at 20 mL/kg/h). Administration of fluids began immediately after baseline measurements were obtained. Hair was then clipped along the ventral aspect of the abdomen, the dog was transported to the operating suite, and the surgical site was prepared aseptically. Surgery was initiated immediately after the 30-minute physiologic data, including video recordings, were obtained. An ovariohysterectomy was performed with a midline celiotomy approach and standard surgical technique. The 60-minute data was collected prior to the completion of surgery in all animals. Recovery was monitored by hospital staff according to standard protocols.

Assessment of microcirculatory variables—On the basis of a consensus report on orthogonal polarization spectral videomicroscope image acquisition and analysis,22 the following variables were derived and assessed from the stored video recordings: total vessel density (mm/mm2), proportion of perfused vessels, MFI, and perfused vessel density (mm/mm2). All values were determined for vessels categorized by diameter (< 20 μm [mostly capillaries], ≥ 20 μm [mostly venules], and all sizes).

Total vessel density determination23 is founded on the principle that vessel density is proportional to the number of vessels crossing arbitrary lines. Three equidistant horizontal lines and 3 equidistant vertical lines are drawn on a representative image of the microvasculature viewed on the computer screen. Vessel density is calculated as the number of vessels crossing the lines divided by the total length of the lines.

Vessel perfusion was categorized as present (continuous blood flow for ≥ 20 seconds), absent (no blood flow detected for ≥ 20 seconds), or intermittent (no blood flow detected for ≥ 50% of the observed interval). The proportion of perfused vessels was then calculated as follows: 100 × (TNV – [number of vessels with absent or intermittent perfusion])/TNV, where TNV denotes the total number of vessels visible in a single field of the videomicroscope. Perfused vessel density, an estimate of functional capillary density, was calculated as TVD × PPV, where TVD represents total vessel density and PPV is the proportion of perfused vessels.

To determine the MFI, video images of the microvasculature viewed on the computer screen were divided into 4 quadrants. A value was assigned on the basis of subjective assessments of the predominant type of blood flow in each quadrant (0 = absent, 1 = intermittent, 2 = sluggish, 3 = normal, and 4 = hyperdynamic). The mean of values for the 4 quadrants was then calculated.24

The total vessel density, proportion of perfused vessels, MFI, and perfused vessel density were acquired by means of computer softwared designed for this purpose. Prior to analysis, the video recordings were assessed for duration, content, focus, illumination, stability, and pressure value. Recordings were subjectively scored on a 3-point scale (0 = excellent, 1 = undesirable but usable, and 2 = unfit for analysis [these were excluded]). The video recordings were analyzed independently and in a blinded manner by 1 experienced video reviewer using the software.

Statistical analysis—Statistical analysis was performed with commercially available software.e,f Mean values derived from analysis of available video recordings were computed for each dog at each measurement time for the 4 microcirculatory variables (total vessel density, perfused vessel density, proportion of perfused vessels, and MFI) for vessels < 20 μm, ≥ 20 μm, and of any diameter; these means were statistically evaluated via weighted repeated-measures ANCOVA with fixed main effects and their interactions for treatment (administration of LRS at 0, 10, or 20 mL/kg/h) and time after anesthetic induction (30 and 60 minutes), with the number of replicates as the weight in the analysis and the corresponding value at baseline as the covariate.

Data for heart rate, blood pressure, Spo2, and CRT were also evaluated via repeated-measures ANCOVA with fixed main effects and their interactions for treatment and time after anesthetic induction (30 and 60 minutes) and with the corresponding value at baseline as the covariate. Because baseline body temperature data were available for only 12 of the 49 dogs, statistical analysis for this variable was based on repeated-measures ANOVA without the use of a covariate.

For microcirculatory and other physiologic variables, mean differences among dogs in the 3 treatment groups overall and at each measurement after baseline were evaluated via Fisher's least significant difference method applied to the LSM obtained via ANCOVA or ANOVA. Additionally, baseline data for the 4 microcirculatory variables for vessels in each size category and the 5 other physiologic variables were summarized as mean ± SD. Pearson correlation coefficients were computed between all pairs of study variables, both within and among microcirculatory and other physiologic variables. Normality of the data was confirmed by means of the Shapiro-Wilk test. Values of P ≤ 0.05 were accepted as significant.

Results

One dog was removed from the study because of excessive pigmentation of the oral mucosa that precluded the ability to interpret videomicroscopic images, resulting in 16 dogs/treatment group. The Petco2 remained in the 35 to 45 mm Hg range at all time points for all dogs. Mean ± SD Petco2 was 38 ± 3 mm Hg at baseline (ie, immediately after anesthetic induction and intubation), 41 ± 4 mm Hg at 30 minutes, and 39 ± 3 mm Hg at 60 minutes. The end-tidal isoflurane concentration was within the 1.3% to 1.5% range for all dogs at all time points; mean ± SD values at baseline, 30 minutes, and 60 minutes were 1.5 ± 0%, 1.4 ± 0.05% and 1.4 ± 0.03%, respectively.

The quality of 64 of 432 video recordings was judged unfit for analysis; 93 of 144 (64.6%) data points were determined by use of all 3 recordings, 40 (27.8%) were determined from 2 recordings, and 11 (7.6%) were established from 1 recording. Summary statistics are reported for baseline microcirculatory variables of dogs by treatment group (0, 10, or 20 mL of LRS/kg/h) and blood vessel diameter (< 20 μm, > 20 μm, and all sizes; Table 1). The LSM ± SE of microcirculatory variables at 30 and 60 minutes after anesthetic induction and the overall values for both postinduction time points are summarized (Table 2).

Table 1—

Mean ± SD baseline data for microcirculatory variables of the buccal mucosa in 48 healthy anesthetized dogs undergoing elective ovariohysterectomy, by treatment group (no IV fluids or IV administration of LRS at 10 or 20 mL/kg/h; n = 16/group) and vessel size.

  Infusion rate (mL/kg/h)
VariableVessel diameter01020
Total vessel density (mm/mm2)
 < 20 μm26.820 ± 5.15627.810 ± 4.41726.440 ± 4.505
 ≥ 20 μm0.513 ± 0.5450.691 ± 0.7880.699 ± 0.594
 All27.330 ± 5.28228.500 ± 4.48527.140 ± 4.736
Perfused vessel density (mm/mm2)
 < 20 μm25.350 ± 5.66026.380 ± 4.43124.320 ± 5.362
 ≥ 20 μm0.047 ± 0.0850.160 ± 0.3080.154 ± 0.273
 All25.400 ± 5.69926.540 ± 4.53724.470 ± 5.423
Proportion of perfused vessels (%)< 20 μm90.930 ± 10.27090.700 ± 5.49087.920 ± 13.750
 ≥ 20 μm1.771 ± 1.8152.347 ± 2.8262.279 ± 2.236
 All92.700 ± 9.23293.050 ± 6.08390.200 ± 13.555
MFI< 20 μm2.680 ± 0.5922.603 ± 0.3532.541 ± 0.636
 ≥ 20 μm2.678 ± 0.4362.559 ± 0.4012.591 ± 0.578
 All2.677 ± 0.4502.572 ± 0.3762.578 ± 0.555

Baseline values were obtained immediately after anesthetic induction and endotracheal intubation. Vessel diameter was measured via softwared used with videomicroscopic images of the buccal mucosa.

Table 2—

Microcirculatory variables (LSM ± SE) for the buccal mucosa of the same dogs in Table 1 by treatment group, vessel size, and time.

   Time after anesthetic induction (min)
VariableInfusion rate (mL/kg/h)Vessel diameter (μm)3060All*
Total vessel density (mm/mm2)0< 2025.563 ± 1.18925.073 ± 1.07925.318 ± 0.876
  ≥ 200.539 ± 0.1350.763 ± 0.1220.651 ± 0.107
  All26.085 ± 1.17625.822 ± 1.06725.954 ± 0.876
 10< 2025.956 ± 1.19023.087 ± 1.14424.522 ± 0.901
  ≥ 200.538 ± 0.1340.745 ± 0.1290.642 ± 0.109
  All26.486 ± 1.17723.837 ± 1.13125.162 ± 0.901
 20< 2023.862 ± 1.11625.310 ± 1.09124.586 ± 0.853
  ≥ 200.890 ± 0.1271.113 ± 0.1241.001 ± 0.104
  All24.737 ± 1.10426.405 ± 1.07925.571 ± 0.852
Perfused vessel density (mm/mm2)0< 2024.013 ± 1.40124.474 ± 1.27124.244 ± 1.048
  ≥ 200.066 ± 0.0590.171 ± 0.0530.119 ± 0.044
  All24.085 ± 1.39924.656 ± 1.26924.371 ± 1.052
 10< 2024.751 ± 1.40521.839 ± 1.35023.295 ± 1.081
  ≥ 200.116 ± 0.0580.248 ± 0.0560.182 ± 0.044
  All24.858 ± 1.40322.086 ± 1.34823.472 ± 1.085
 20< 2023.836 ± 1.31724.410 ± 1.28824.123 ± 1.023
  ≥ 200.187 ± 0.0550.357 ± 0.053§0.272 ± 0.042§
  All24.013 ± 1.31524.756 ± 1.28624.384 ± 1.027
Proportion of perfused vessels (%)0< 2089.187 ± 3.16791.141 ± 2.87090.164 ± 2.173
  ≥ 202.022 ± 0.7693.719 ± 0.6962.870 ± 0.570
  All90.855 ± 2.75494.652 ± 2.49792.753 ± 1.901
 10< 2092.270 ± 3.16689.191 ± 3.04690.731 ± 2.234
  ≥ 201.750 ± 0.7663.082 ± 0.7362.416 ± 0.583
  All94.079 ± 2.75892.294 ± 2.65193.187 ± 1.958
 20< 2092.454 ± 2.97787.205 ± 2.91089.830 ± 2.121
  ≥ 203.307 ± 0.7194.173 ± 0.7033.740 ± 0.553
  All95.882 ± 2.58991.511 ± 2.53193.697 ± 1.855
MFI0< 202.854 ± 0.1452.983 ± 0.1322.918 ± 0.100
  ≥ 202.834 ± 0.0903.049 ± 0.0822.941 ± 0.067
  All2.837 ± 0.0953.045 ± 0.0862.941 ± 0.070
 10< 202.717 ± 0.1452.855 ± 0.1402.786 ± 0.103
  ≥ 202.790 ± 0.0902.884 ± 0.0862.837 ± 0.069
  All2.772 ± 0.0952.890 ± 0.0912.831 ± 0.071
 20< 202.858 ± 0.1362.755 ± 0.1332.806 ± 0.097
  ≥ 202.868 ± 0.0852.889 ± 0.0832.878 ± 0.065
  All2.865 ± 0.0892.854 ± 0.0872.859 ± 0.068

Values were assessed by means of repeated-measures ANCOVA with the corresponding value at baseline as the covariate.

Category represents the overall means for 30- and 60-minute time points combined.

Within a column for a given variable, value differs significantly (P < 0.05) from that for vessels of the same size in the 10 mL/kg/h treatment group.

Within a column for a given variable, value differs significantly from that for vessels of the same size in the 0 and 10 mL/kg/h treatment groups.

Within a column for a given variable, value differs significantly from that for vessels of the same size in the 0 mL/kg/h group.

For vessels < 20 μm in diameter and for vessels of all sizes combined, total vessel density did not differ significantly among the 3 treatment groups at any times evaluated. However, significant (P = 0.030) differences for vessels ≥ 20 μm in diameter were found among the 3 treatment groups, and the overall mean for vessels of this size in dogs of the 20 mL/kg/h group (1.001 mm/mm2) was significantly greater than that for dogs of the 0 mL/kg/h (0.651 mm/mm2; P = 0.024) and 10 mL/kg/h (0.642 mm/mm2; P = 0.021) groups. Total vessel density for vessels ≥ 20 μm in diameter also differed significantly (P = 0.012) between the 30- and 60-minute measurements; however, no consistent differences were observed among the 3 treatment groups with respect to time. The treatment-by-time interactions for vessels in each size category were nonsignificant (P > 0.25) for this variable.

Similarly, perfused vessel density for vessels < 20 μm in diameter and for vessels of all sizes combined did not differ significantly among the 3 treatment groups at any evaluated time points (Table 2). However, the overall mean perfused vessel density for vessels ≥ 20 μm in diameter differed significantly (P = 0.016) between the 20 mL/kg/h (0.272 mm/mm2) and 0 mL/kg/h groups (0.119 mm/mm2). Additionally, there was a significant (P = 0.016) linear trend in perfused vessel density versus infusion rate for vessels of this size. Although perfused vessel density for vessels ≥ 20 μm in diameter was significantly (P = 0.002) different between the 30- and 60-minute time points, consistent differences were not observed among the treatment groups with respect to time, and the treatment-by-time interaction for this variable was nonsignificant (P > 0.25) for each vessel size category.

Neither the proportion of perfused vessels nor MFI varied significantly among treatment groups with respect to vessels < 20 μm, ≥ 20 μm, and of any diameter at any of the time points evaluated (Table 2). The treatment-by-time interaction for each of these variables was nonsignificant (P > 0.25) for vessels in each size category. The mean proportion of perfused vessels ≥ 20 μm in diameter differed significantly (P = 0.019) overall (when all treatment groups were considered) between the 30- and 60-minute measurements.

Summary statistics for the remaining physiologic variables are reported for each of the 3 treatment groups at baseline (Table 3). The LSM ± SE values for each treatment group at 30 and 60 minutes after anesthetic induction and the overall values for both postinduction time points are indicated (Table 4).

Table 3—

Mean ± SD baseline measurements for selected physiologic variables of the same dogs in Table 1 by treatment group.

 Infusion rate (mL/kg/h)
Variable01020
Heart rate (beats/min)84 ± 2379 ± 1578 ± 24
Blood pressure (mm Hg)106 ± 14111 ± 14105 ± 9
Spo2 (%)98.1 ± 1.798.3 ± 1.797.6 ± 1.3
CRT (s)1.50 ± 0.001.47 ± 0.131.47 ± 0.13
Body temperature (°C)36.33 ± 0.4936.53 ± 1.3037.02 ± 0.57

Body temperature was recorded for 4 dogs/group; remaining data were reported for all 16 dogs in each group. Blood pressure was measured with a Doppler flow detector.

Table 4—

Selected physiologic variables (LSM ± SE) for the same dogs in Table 1 by treatment group and time.

  Time after anesthetic induction (min)
VariableInfusion rate (mL/kg/h)3060All*
Heart rate (beats/min)078 ± 469 ± 473 ± 3
 1075 ± 482 ± 478 ± 3
 2079 ± 478 ± 479 ± 3
Blood pressure (mm Hg)0108 ± 5113 ± 5110 ± 4
 1097 ± 5107 ± 5102 ± 4
 20104 ± 5110 ± 5107 ± 4
Spo2 (%)098.4 ± 0.497.9 ± 0.498.1 ± 0.3
 1098.0 ± 0.498.2 ± 0.497.8 ± 0.3
 2097.9 ± 0.497.6 ± 0.497.8 ± 0.3
CRT (s)01.49 ± 0.021.49 ± 0.021.49 ± 0.02
 101.45 ± 0.021.45 ± 0.021.45 ± 0.02
 201.48 ± 0.021.51 ± 0.021.49 ± 0.02
Body temperature (°C)036.09 ± 0.3335.70 ± 0.2735.89 ± 0.21
 1035.62 ± 0.2835.29 ± 0.2735.45 ± 0.20
 2035.67 ± 0.3135.46 ± 0.2635.56 ± 0.21

Values for heart rate, blood pressure, Spo2, and CRT were assessed by means of repeated-measures ANCOVA with the corresponding value at baseline as the covariate; body temperature data were compared via repeated-measures ANOVA.

Category represents the overall means for 30- and 60-minute time points combined.

Within a column for a given variable, value is significantly (P < 0.05) different from that in the 0 mL/kg/h group.

Within a column for a given variable, value differs significantly from that for vessels of the same size in the 10 mL/kg/h treatment group.

Overall mean heart rate did not differ significantly among the 3 treatment groups (Table 4). A significant (P = 0.020) interaction was observed between the main effects of treatment and time for this variable. Mean heart rate was similar among groups 30 minutes after anesthetic induction but was significantly (P = 0.025) higher in the 10 mL/kg/h group than in the 0 mL/kg/h group 60 minutes after induction (82 vs 69 beats/min).

Overall mean Doppler-measured blood pressure was also similar among treatment groups (Table 4). Further, although a significant (P = 0.011) increase in blood pressure was observed with respect to time, no significant differences for this variable were found among the treatment groups over time, and the treatment-by-time interaction was not significant (P = 0.65).

Fourteen dogs (6 in the 0 mL/kg/h group and 4 each in the 10 and 20 mL/kg/h groups) required IV bolus administration of LRS because of Doppler-measured blood pressure < 90 mm Hg. All dogs had normalization of blood pressure following this treatment, and none required > 1 bolus. The treatment caused the cumulative dose of fluids in affected dogs to increase by 15 mL/kg during the study hour. None of the IV fluid boluses was given during microvideoscopic image acquisition; boluses were administered at a mean time of 30 minutes (range, 10 to 40 minutes) after baseline measurements were obtained. The LSM values for all recorded data of the 34 dogs that did not receive a fluid bolus did not differ significantly from that of the larger group (data not shown).

Mean Spo2 differed by ≤ 0.5% among treatment groups overall and at the 30- and 60-minute time points (Table 4). Differences in Spo2 were nonsignificant (P > 0.55) with respect to time and treatment. Mean CRT was also not significantly (P = 0.183) different overall among groups but was significantly higher (P = 0.032) in the 20 mL/kg/h group than in the 10 mL/kg/h group 60 minutes after induction (1.51 vs 1.45 seconds). No significant differences in body temperature were observed with respect to either treatment or time (P > 0.15).

Significant correlation was identified among the microcirculatory variables for vessels < 20 μm in diameter, as expected (r = 0.24 to 0.92; P < 0.005 for all). Additionally, blood pressure and CRT had a significant but weak positive correlation with both the total diameter (r = 0.248; P = 0.003) and perfused diameter (r = 0.205; P = 0.014) for vessels of this size, and CRT had a significant but weak negative correlation with Spo2 (r = −0.213; P = 0.010).

Discussion

Intravenous fluid administration during anesthesia is commonly recommended to counteract anesthetic-induced vasodilation; to prevent or treat hypotension, hypovolemia, and decreased tissue perfusion; and to help maintain renal function.9 Arterial blood pressure is commonly monitored as an indicator of perfusion in anesthetized small animals, although some research suggests that arterial blood pressure (and central venous pressure) does not adequately correlate with cardiac output and tissue perfusion.25–32 Goal-directed methods of titrating fluid administration have been proposed, including monitoring and adjustment for pulse pressure variation and mixed venous oxygen saturation.33,34 However, these variables cannot assess microcirculatory blood flow but instead provide a more global assessment of macrocirculatory flow.12 Several studies have found a lack of clear association between macrohemodynamic variables and measures of microcirculatory perfusion.35–38 Additionally, microcirculatory derangements in humans undergoing surgery were found to be associated with development of postoperative complications.35 The use of propofol has been associated with a decrease in mean arterial blood pressure, systemic vascular resistance,39 and microvascular density in people,40 and alterations in oxygen extraction capabilities in dogs.41 However, dogs in the present study had no detectable decrease in microvascular density or flow, perhaps because of species differences, variations in overall health, or the multimodal induction protocol that was used. Since baseline measurements were obtained immediately after induction and endotracheal intubation, it is possible that sympathetic stimulation during intubation or vasodilation immediately after initiating isoflurane delivery could have affected the baseline values; however, this was not apparent on examination of the macro- and microcirculatory data.

We did not find a significant association between IV fluid administration and perfusion (proportion of perfused vessels) or blood flow (MFI) in vessels < 20 μm in diameter in healthy dogs anesthetized for elective ovariohysterectomy. However, for vessels ≥ 20 μm in diameter, dogs that received 20 mL of LRS/kg/h had significantly greater total vessel density, compared with dogs that received 0 or 10 mL/kg/h of LRS, and perfused vessel density, compared with dogs that received no LRS. These larger vessels are most likely arterioles and venules that supply blood to and from the capillaries, respectively, and are therefore vitally important for organ perfusion. Given that capillaries are not able to dilate or constrict, the only way the circulatory system can adjust flow to the capillaries is through vasodilation or vasoconstriction of these larger microcirculatory vessels. It is therefore plausible that the greater venular or arteriolar density and perfusion was a response to accommodate increased intravascular volume and shunt additional blood flow, if it was not needed for tissue perfusion and could cause harmful increases in capillary hydrostatic pressures. This observation may also have been attributable to the use of LRS. Most formulations of LRS, including the product used in the present study, contain a racemic mixture of the d-lactate and l-lactate isomers. Given that l-lactate is naturally produced during metabolism in small animals, it is a more natural and perhaps benign method of alkalinization of fluids intended for IV administration. The d-lactate isomer has been found to increase leukocyte production of reactive oxygen species, and the racemic mixture may alter expression of genes to increase apoptosis.42 Neurocardiac toxic effects have been described in rats that were experimentally administered LRS with d-lactate, compared with those that received only LRS with l-lactate only.43 It would be interesting to study the effects of an enantiomerically pure preparation of LRS on the microcirculation of dogs during inhalant anesthesia.

It is possible that the LRS administered in the present study induced recruitment and dilation of venules and arterioles in a rate-dependent manner, which may benefit perfusion (by increasing total and perfused vessel density of venules) and also prevent excessive increases in hydrostatic pressure. High hydrostatic pressures can lead to increased interstitial volumes, as seen in swine used in a model of hemorrhagic shock to compare resuscitation with saline (0.9% NaCl) solution versus LRS.44 In that study, swine that received LRS had less extravascular lung water and higher blood pressures than did those that received saline solution, although global end diastolic volumes and stroke volumes were similar among groups. This suggests that LRS may somehow prevent leakage of intravascular fluid into the surrounding interstitium, despite its possible proinflammatory effect, perhaps through dilation of venules and arterioles.

It has been shown that hypercapnia can cause selective venular dilation,45 but this was not likely to have contributed to the findings in our study. The Petco2 of all dogs in the present study was monitored, and dogs were manually or mechanically ventilated to keep the Petco2 between 35 and 45 mm Hg. However, because arterial blood gas analysis was not performed, it is possible that some dogs developed hypercapnia that was not detected with the monitoring tools used. Given that the significant differences in total and perfused vessel density were identified in dogs of the highest infusion rate group, hypercapnia was considered less plausible as the cause of venular dilation.

Overall measurements for cardiopulmonary variables, including heart rate, CRT, Spo2, and body temperature, were not significantly different between treatment groups, and no differences were considered clinically relevant. A significant (P = 0.011) increase in blood pressure was observed with respect to time, but this also likely had minimal clinical relevance because all mean values were within the reference range. The lack of clinically relevant changes in heart rate and blood pressure in response to fluid administration in well-hydrated, anesthetized dogs is in agreement with the recent findings of Muir et al.21 There were no changes in macrocirculatory variables that corresponded with the increase in density and perfusion of venules and arterioles in dogs that received LRS at the highest infusion rate in our study. Therefore, the importance of these findings remains largely unknown, but it is plausible that recruitment of vessels leading to capillary beds would be desirable to maximize delivery of blood and oxygen to these regions and may also prevent over-perfusion of small capillary vessels, thus serving as a reservoir to accommodate increases in blood volume. Dogs that received 0 or 10 mL of fluids/kg/h did not have evidence of venule or arteriole (vessels ≥ 20 μm in diameter) recruitment, which may suggest that dogs receiving such treatments could be more vulnerable to hypoxia during periods of hypotension. However, the total and perfused vessel density of vessels ≥ 20 μm in diameter were near or above the reported range for healthy dogs in all groups, so the differences may not be clinically important.46 It is also possible that the anesthesia protocol induced changes in the microcirculation and that the 20 mL of LRS/kg/h enabled greater recruitment of vessel capacity.

Although the importance of the specific results for the present study is uncertain, this does not mean that administration of IV fluids to anesthetized dogs is unimportant. Almost one-third of the dogs in the study (n = 14) required bolus administration of LRS for treatment of hypotension (blood pressure < 90 mm Hg47), regardless of the fluid administration rate. This is similar to the incidence of hypotension reported in a large retrospective study11 of almost 1,300 anesthetized dogs by Redondo et al. All dogs in our study that received bolus fluid administration had a subsequent increase in blood pressure, so the fluid bolus appeared to improve blood pressure and presumably perfusion to the tissues. The alterations in blood pressure suggested variation among the dogs' responses and sensitivity to anesthesia, or that some dogs required slightly greater amounts of anesthetic than others during the procedure. This finding could also have been related to hydration status prior to surgery. Although the hydration status of dogs was deemed adequate upon hospitalization, there may have been some mild differences that were undetected. The animals in the present study were client-owned, and most were hospitalized overnight prior to surgery. Dogs with anxiety because of hospitalization may have been less likely to eat or drink well prior to removal of food and water at midnight in preparation for general anesthesia the next day. In our opinion, such short-term stress was unlikely to have caused major changes in intravascular volume, but may have had a small influence on cardiovascular stability or derangements during anesthesia that were fluid-responsive. After 10 hours of fasting, healthy human patients continued to have blood volume and plasma volume within the respective reference ranges48; we consider it unlikely that healthy dogs would have different results. It is unknown whether the administration of a fluid bolus prior to anesthetic induction might reduce the incidence of hypotension during anesthesia, even in dogs that are apparently well-hydrated. However, in a study49 of human surgical patients undergoing spinal anesthesia, a 20 mL/kg bolus of LRS was found to prevent anesthetic-induced adverse cardiovascular effects. The most plausible cause of intraoperative hypotension in our study was the use of vasodilatory drugs, primarily acepromazine, propofol, and isoflurane, in the protocol.

Because it would not have been ethically appropriate to withhold fluid therapy in patients that developed hypotension, it is unknown whether these dogs would eventually have a significant decrease in microcirculatory variables if untreated. The episodes of hypotension and bolus fluid administration did not occur at the 30- or 60-minute measurement time points in any of the dogs; therefore, it was not possible to assess associations between microcirculatory variables and the hypotensive events. Humans with sepsis are not always capable of appropriately compensating for a decrease in blood pressure during surgery,50 and this may be true of dogs that are ill or anesthetized for compulsory surgery. It is also unknown whether microcirculatory perfusion to the head, including oral mucous membranes, was preserved at the cost of perfusion to less vital capillary beds that were not evaluated in our study.

It is possible that fluid administration rates higher than those used in this study might have resulted in greater changes in microcirculatory variables, but given that the micro- and macrocirculatory variables were not considered abnormal in any of the treatment groups, this may not be indicated. In a recent study,21 anesthetized dogs treated with 30 mL of LRS/kg/h did not have detectable changes in oxygen delivery to the tissues, compared with dogs that were given no fluids or that received LRS at lower administration rates.

Potential limitations of the present study include the small sample size and inability to analyze almost 15% of the video recordings acquired because of quality concerns, imaging limitations (eg, inability to assess variables in dogs with pigmented mucosa), and the potential for a type II error. In addition, the oral mucosa may not be representative of the microcirculatory perfusion to other vital organ tissue beds and the results of this study must therefore be interpreted accordingly.

Future studies might further investigate the use of liberal versus restrictive IV fluid treatments and include microcirculatory evaluation of organs such as the kidneys or parts of the gastrointestinal tract to provide further assessment of microcirculatory blood flow to vital organs during general anesthesia. In addition, evaluation of markers of organ dysfunction following anesthesia might be valuable in assessment of complications secondary to fluid administration, such as acute gastrointestinal or renal injury, cardiac arrhythmias or changes in systolic function, wound healing, or alterations in pulmonary function. Examining the importance of routine fluid administration in anesthetized dogs with sepsis or severe inflammatory diseases may also reveal different requirements. Lastly, future studies investigating the effects of various types of fluids during anesthesia, including other crystalloids, synthetic colloids, and blood products, may prove informative and useful.

ABBREVIATIONS

CRT

Capillary refill time

LRS

Lactated Ringer's solution

LSM

Least squares mean

MFI

Microcirculatory flow index

Petco2

End-tidal partial pressure of CO2

Spo2

Oxygen saturation as measured by pulse oximetry

a.

King F2, Kingsystems, Noblesville, Ind.

b.

Lactated Ringer's solution, USP, Hospira, Lake Forest, Ill.

c.

MicroScan videomicroscope, MicroVision Medical, Amsterdam, The Netherlands.

d.

AVA, version 3.0, MicroScan Analysis Software, MicroVision Medical, Amsterdam, The Netherlands.

e.

SAS, version 9.2, SAS Institute, Cary, NC.

f.

Minitab, Release 14, Minitab Inc, State College, Pa.

References

  • 1. Davis H, Jensen T, Johnson A, et al. 2013 AAHA/AAFP fluid therapy guidelines for dogs and cats. J Am Anim Hosp Assoc 2013; 49: 149159.

  • 2. Shires T, Williams J, Brown F. Acute change in extracellular fluids associated with major surgical procedures. Ann Surg 1961; 154: 803810.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Wilson BJ, Adwan KO. A critical assessment of the use of blood transfusions during major gastric operations. Arch Surg 1960; 80: 760767.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Keane PW, Murray PF. Intravenous fluids in minor surgery. Their effect on recovery from anaesthesia. Anaesthesia 1986; 41: 635637.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Terry RN, Trudnowski RJ. Intraoperative fluid therapy: relationship to anesthetic and surgical complications. N Y State J Med 1964; 64: 26462654.

    • Search Google Scholar
    • Export Citation
  • 6. Thangathurai D, Charbonnet C, Wo CC, et al. Intraoperative maintenance of tissue perfusion prevents ARDS. Adult Respiratory Distress Syndrome. New Horiz 1996; 4: 466474.

    • Search Google Scholar
    • Export Citation
  • 7. Campbell IT, Baxter JN, Tweedie IE, et al. IV fluids during surgery. Br J Anaesth 1990; 65: 726729.

  • 8. Arkiliç CF, Taguchi A, Sharma N, et al. Supplemental perioperative fluid administration increases tissue oxygen pressure. Surgery 2003; 133: 4955.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Kudnig ST, Mama K. Perioperative fluid therapy. J Am Vet Med Assoc 2002; 221: 11121121.

  • 10. Gaynor JS, Dunlop CI, Wagner AE, et al. Complications and mortality associated with anesthesia in dogs and cats. J Am Anim Hosp Assoc 1999; 35: 1317.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Redondo JI, Rubio M, Soler G, et al. Normal values and incidence of cardiorespiratory complications in dogs during general anaesthesia. A review of 1281 cases. J Vet Med A Physiol Pathol Clin Med 2007; 54: 470477.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Gaynor JS, Wertz EM, Kesel LM, et al. Effect of intravenous administration of fluids on packed cell volume, blood pressure, and total protein and blood glucose concentrations in healthy halothane-anesthetized dogs. J Am Vet Med Assoc 1996; 208: 20132015.

    • Search Google Scholar
    • Export Citation
  • 13. Muir WW III, Wiese AJ. Comparison of lactated Ringer's solution and a physiologically balanced 6% hetastarch plasma expander for the treatment of hypotension induced via blood withdrawal in isoflurane-anesthetized dogs. Am J Vet Res 2004; 65: 11891194.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Mensack S. Fluid therapy: options and rational administration. Vet Clin North Am Small Anim Pract 2008; 38: 575586.

  • 15. Aarnes TK, Bednarski RM, Lerche P, et al. Effect of intravenous administration of lactated Ringer's solution or hetastarch for the treatment of isoflurane-induced hypotension in dogs. Am J Vet Res 2009; 70: 13451353.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Holte K, Sharrock NE, Kehlet H. Pathophysiology and clinical implications of perioperative fluid excess. Br J Anaesth 2002; 89: 622632.

  • 17. Holte K, Kehlet H. Fluid therapy and surgical outcomes in elective surgery: a need for reassessment in fast-track surgery. J Am Coll Surg 2006; 202: 971989.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Brandstrup B. Fluid therapy for the surgical patient. Best Pract Res Clin Anaesthesiol 2006; 20: 265283.

  • 19. Bjorling DE, Rawlings CA. Relationship of intravenous administration of Ringer's lactate solution to pulmonary edema in halothane-anesthetized cats. Am J Vet Res 1983; 44: 10001006.

    • Search Google Scholar
    • Export Citation
  • 20. Warthen HJ. Massive intravenous injections: an experimental study. Arch Surg 1935; 30: 199227.

  • 21. Muir WW, Kijtawornrat A, Ueyama Y, et al. Effects of intravenous administration of lactated Ringer's solution on hematologic, serum biochemical, rheological, hemodynamic, and renal measurements in healthy isoflurane-anesthetized dogs. J Am Vet Med Assoc 2011; 239: 630637.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. De Backer D, Hollenberg S, Boerma C, et al. How to evaluate the microcirculation: report of a round table conference. Crit Care 2007; 11: R101.

  • 23. De Backer D, Creteur J, Preiser JC, et al. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 2002; 166: 98104.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Boerma EC, Mathura KR, van der Voort PH, et al. Quantifying bedside-derived imaging of microcirculatory abnormalities in septic patients: a prospective validation study. Crit Care 2005; 9: R601R606.

    • Search Google Scholar
    • Export Citation
  • 25. Chappell D, Jacob M, Hofmann-Kiefer K, et al. A rational approach to perioperative fluid management. Anesthesiology 2008; 109: 723740.

  • 26. Magder S. Central venous pressure monitoring. Curr Opin Crit Care 2006; 12: 219227.

  • 27. Renner J, Scholz J, Bein B. Monitoring fluid therapy. Best Pract Res Clin Anaesthesiol 2009; 23: 159171.

  • 28. Kimberger O, Arnberger M, Brandt S, et al. Goal-directed colloid administration improves the microcirculation of healthy and perianastomotic colon. Anesthesiology 2009; 110: 496504.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Hiltebrand LB, Pestel G, Hager H, et al. Perioperative fluid management: comparison of high, medium and low fluid volume on tissue oxygen pressure in the small bowel and colon. Eur J Anaesthesiol 2007; 24: 927933.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Johansen LB, Bie P, Warberg J, et al. Hemodilution, central blood volume, and renal responses after an isotonic saline infusion in humans. Am J Physiol 1997; 272: R549R556.

    • Search Google Scholar
    • Export Citation
  • 31. Cornelius LM, Finco DR, Culver DH. Physiologic effects of rapid infusion of Ringer's lactate solution into dogs. Am J Vet Res 1978; 39: 11851190.

    • Search Google Scholar
    • Export Citation
  • 32. Boscan P, Pypendop BH, Siao KT, et al. Fluid balance, glomerular filtration rate, and urine output in dogs anesthetized for an orthopedic surgical procedure. Am J Vet Res 2010; 71: 501507.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Renner J, Cavus E, Meybohm P, et al. Pulse pressure variation and stroke volume variation during different loading conditions in a paediatric animal model. Acta Anaesthesiol Scand 2008; 52: 374380.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Hiltebrand LB, Kimberger O, Arnberger M, et al. Crystalloids versus colloids for goal-directed fluid therapy in major surgery. Crit Care 2009; 13: R40.

  • 35. Jhanji S, Lee C, Watson D, et al. Microvascular flow and tissue oxygenation after major abdominal surgery: association with post-operative complications. Intensive Care Med 2009; 35: 671677.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. De Backer D, Creteur J, Dubois MJ, et al. Microvascular alterations in patients with acute severe heart failure and cardiogenic shock. Am Heart J 2004; 147: 9199.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Trzeciak S, Dellinger RP, Parrillo JE, et al. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med 2007; 49: 8898.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38. Trzeciak S, McCoy JV, Phillip DR, et al. Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med 2008; 34: 22102217.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39. Baraka A, Dabbous A, Siddik S, et al. Action of propofol on resistance and capacitance vessels during cardiopulmonary bypass. Acta Anaesthesiol Scand 1991; 35: 545547.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40. Koch M, De Backer D, Vincent JL, et al. Effects of propofol on human microcirculation. Br J Anaesth 2008; 101: 473478.

  • 41. Van der Linden P, Schmartz D, Gilbart E, et al. Effects of propofol, etomidate, and pentobarbital on critical oxygen delivery. Crit Care Med 2000; 28: 24922499.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42. Koustova E, Stanton K, Gushchin V, et al. Effects of lactated Ringer's solutions on human leukocytes. J Trauma 2002; 52: 872878.

  • 43. Chan L, Slater J, Hasbargen J, et al. Neurocardiac toxicity of racemic d,l-lactate fluids. Integr Physiol Behav Sci 1994; 29: 383394.

  • 44. Phillips CR, Vinecore K, Hagg DS, et al. Resuscitation of haemorrhagic shock with normal saline vs. lactated Ringer's: effects on oxygenation, extravascular lung water and haemodynamics. Crit Care 2009; 13: R30.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45. Yamaguchi K, Suzuki K, Naoki K, et al. Response of intra-acinar pulmonary microvessels to hypoxia, hypercapnic acidosis, and isocapnic acidosis. Circ Res 1998; 82: 722728.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46. Silverstein DC, Pruett-Saratan A, Drobatz KJ. Measurements of microvascular perfusion in healthy anesthetized dogs using orthogonal polarization spectral imaging. J Vet Emerg Crit Care (San Antonio) 2009; 19: 579587.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47. Haskins SC. Monitoring the anesthetized patient. In: Thurman JC, Tranquilli WJ, Benson GJ, eds. Lumb and Jones' veterinary anesthesia and analgesia. 4th ed. Philadelphia: Wiley-Blackwell, 2007; 533560.

    • Search Google Scholar
    • Export Citation
  • 48. Jacob M, Chappell D, Conzen P, et al. Blood volume is normal after pre-operative overnight fasting. Acta Anaesthesiol Scand 2008; 52: 522529.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49. Mojica JL, Melendez HJ, Bautista LE. The timing of intravenous crystalloid administration and incidence of cardiovascular side effects during spinal anesthesia: the results from a randomized controlled trial. Anesth Analg 2002; 94: 432437.

    • Search Google Scholar
    • Export Citation
  • 50. Trzeciak S, Rivers EP. Clinical manifestations of disordered microcirculatory perfusion in severe sepsis. Crit Care 2005; 9(suppl 4):S20S26.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 82 0 0
Full Text Views 2052 1534 137
PDF Downloads 419 162 14
Advertisement