Incisional Block With Bupivacaine for Analgesia After Celiotomy in Dogs
A blind, placebo-controlled clinical trial was performed to evaluate the postoperative analgesic effect of preoperative infiltration of the incision site with bupivacaine in dogs undergoing celiotomy. Sixty dogs were randomly allocated into four groups: preoperative bupivacaine, postoperative bupivacaine, preoperative saline, and postoperative saline. All dogs were premedicated with acepromazine and meperidine; then they were anesthetized with thiopentone and isoflurane. Each group received either bupivacaine or normal saline before midline incision or just before skin closure. After surgery, pain scores were assigned using a numerical rating scale. Preoperative bupivacaine was associated with significantly lower pain scores and a significantly lower need for opioid administration. The authors conclude that a preoperative incisional block with bupivacaine seems to be a useful adjunct for controlling pain after celiotomy in dogs.
Introduction
Celiotomy is a common surgical procedure performed in small animals, because many surgical interventions for various body systems require access to the abdominal cavity. Effective analgesia after celiotomy is a challenging task for the anesthesiologist, and many analgesic protocols have been developed for postoperative pain management in small animals. Opioids, nonsteroidal antiinflammatory drugs (NSAIDs), and various other analgesics may be administered systemically or epidurally in dogs.1 Although most of these drugs have remarkable analgesic properties, they also have side effects. Local anesthetics offer some advantages, such as potent analgesia by regional blockade, no legal control, and lower cost.
In people, local anesthesia via wound infiltration has been proposed as an effective analgesic technique for some types of hernia repair, including inguinal herniorrhaphy2,3 and groin crease incision.4 Tissue infiltration before skin incision can effectively provide preemptive analgesia in many cases of elective surgery, such as inguinal herniorrhaphy,5 appendectomy, 6 and tonsillectomy,7 as well as in some human orthopedic procedures. 8,9 However, this is not always the case. Preoperative administration of bupivacaine did not offer any advantage over its postoperative administration after breast biopsy,10 and pre-or postoperative ropivacaine did not improve analgesia after breast surgery.11,12
The situation is rather confusing in abdominal surgery, because the conclusions of many clinical trials in people have been controversial. In one study, bupivacaine was shown to offer preemptive analgesia after laparoscopic gynecological examination;13 but in another study, bupivacaine did not reduce pain or opioid requirements after gynecological laparoscopy.14 Preoperative infiltration of the surgical area with bupivacaine improved both immediate and late analgesia and reduced analgesic requirements after abdominal hysterectomy (compared with placebo).15 Postoperative wound infiltration with bupivacaine was also shown to reduce incisional pain for at least 24 hours after caesarean section in women, although it did not reduce secondary hyperalgesia.16 Other studies in people have not demonstrated any analgesic-sparing effects of bupivacaine or ropivacaine in patients undergoing abdominal hysterectomy or caesarean section.17–21
The results from human studies are not directly applicable to veterinary medicine because of species differences in anatomy and posture, and only limited veterinary reports address the effectiveness of local anesthesia on analgesia after celiotomy. The authors of one study reported that bupivacaine provided effective analgesia after ovariohysterectomy in dogs when administered intraperitoneally and at the incision site. The incisional anesthesia was via a “splash” onto the subcutaneous tissues after complete closure of the linea alba but before skin closure.22 A swine model of surgery and stress provided evidence that an isotonic mixture of lidocaine and bupivacaine could block spinal nociception after experimental celiotomy. This mixture was applied by a combination of wound infiltration of the skin and muscles within the surgical area and soaking of the peritoneum before incision.23
The aim of the current study was to evaluate the effectiveness of preemptive incisional block with bupivacaine on postoperative pain and opioid requirements after celiotomy in dogs.
Materials and Methods
Animals
The study population consisted of 60 dogs that were presented for midline celiotomy. Dogs with severe systemic manifestations of disease (i.e., American Society of Anesthesiologists [ASA] physical status >3) were excluded. The dogs were hospitalized at least 1 day before and 1 day after the surgery. In all cases, informed consent was obtained from the owners or caretakers. The study was approved by the Clinic’s Ethics Committee.
Study Design
On admission, each dog was randomly assigned to one of four treatment groups (15 dogs per group): 1) bupivacaine preoperatively (B-pre), 2) bupivacaine postoperatively (Bpost), 3) normal saline preoperatively (NS-pre), and 4) normal saline postoperatively (NS-post). The order of treatment was assigned via a computerized random-number algorithm, with the researchers blinded to this assignment.
Anesthesia and Surgery
All dogs were fasted for approximately 8 hours before anesthesia, with access to water withdrawn 2 hours before induction. Each dog was premedicated with acepromazinea (0.05 mg/kg intramuscularly [IM]) and meperidineb (3 mg/kg IM) approximately 30 minutes before induction with thiopentonec (6 to 8 mg/kg intravenously [IV]). Additional dosages of thiopentone at 1 to 2 mg/kg were administered as needed to facilitate tracheal intubation, and the total thiopentone dose (in mg/kg) was recorded. Anesthesia was maintained with isofluraned in oxygen at an end-tidal concentration of 1.6% to 2.1%. No other routine analgesic drugs were used throughout surgery. Any dogs requiring additional analgesia during anesthesia were excluded from the study. A continuous IV drip of lactated Ringer’s solution (10 mL/kg per hour) was maintained during the procedure.
Dogs were monitored from induction to discontinuation of anesthesia using a standard protocol that included systolic, diastolic, and mean arterial blood pressures;e electrocardiogram; oxygen saturation as measured by pulse oximetry (SpO2);e inspired and end-tidal carbon dioxide (CO2);f isoflurane concentration;f oxygen percentage;f and respiratory rate.f Mean arterial blood pressure was measured using the indirect oscillometric method. The gas analyzer was calibrated appropriately.
Celiotomy was performed through a ventral midline incision. Indications for celiotomy are given in Table 2. In the B-pre and NS-pre groups, 0.8 mL/kg bupivacaineg 0.25% (i.e., 2 mg/kg) or normal saline was injected subcutaneously (SC) and IM at the incision site just before the start of the incision. The B-post and NS-post groups had the same volume of bupivacaine or normal saline similarly injected after subcutaneous closure. The needle was inserted at the one end of the incision and aspirated for blood, and then bupivacaine or saline was injected in a fan-like fashion to infiltrate subcutaneous and muscular tissues. Then the needle was repositioned a slight distance away, and the bupivacaine or saline injection was repeated. This procedure was repeated until the entire length of the incision site was infiltrated.24
The same surgeon performed all the surgeries. Abdominal closure was performed in three layers (i.e., abdominal wall, subcutis, and skin) using the same suture materials, patterns, and knots for all cases. Skin was closed appropriately using an intradermal pattern, and the length of the incision was measured after skin closure.
Blinding of the trial was maintained by having a single anesthesiologist, who was not involved in the anesthetic process, prepare the drug solutions. The surgeon was blinded to the type of drug injected, as was the anesthesiologist monitoring the animal. As an added precaution, the anesthesiologist monitoring the animal left the operating room for a few minutes during infiltration of the incision site (i.e., just before the incision and just before skin closure) in all cases. After skin closure, anesthesia was discontinued, and the dogs were placed in cages for the next 24 hours.
Pain and Sedation Assessment
Each dog received continuous nursing care for at least 24 hours. Any signs of suffering or pain were immediately reported, and the anesthesiologist in charge was notified. Rapid-acting analgesics were administered if needed. Pain was scored at 1, 2, 3, 4, 5, 6, 16 to 20, and 24 hours after surgery, using a 0 to 10 numerical rating scale (0=no pain, 10=worst pain imaginable). Sedation was scored at the same time intervals, using a discontinuous scoring system (0=fully alert, 1=alert but unable to walk, 2=drowsy and unable to stand, 3=heavily sedated/asleep). This discontinuous scoring system was used rather than a numerical or visual analogue scale, because accurate quantitative assessment of sedation was not among the aims of this study.
Pain and sedation were evaluated and scores were assigned by the same experienced anesthesiologist on all occasions. Pain and sedation scores were based on behavioral criteria. An initial assessment of each dog’s temperament and personality was made before premedication. After surgery, the dog was observed while undisturbed inside the cage. Then the researcher approached the dog and communicated verbally. The dog’s posture, behavior, vocalization, and food and water consumption were noted. Shortly thereafter, the dog was encouraged to walk, and its willingness to move and the pattern of locomotion were recorded. Finally, the dog was gently handled, and the incision area (i.e., approximately 5 cm around the wound) was palpated by applying firm finger pressure. The overall behavioral response was assessed, and the estimated degrees of pain and sedation were scored.25,26 Whenever the pain score was above 5, fentanylh (2 μg/kg IV) and morphinei (0.1 to 0.3 mg/kg IM) were administered for analgesia.
Data Analysis
The Shapiro-Wilk test of normality was used to evaluate the distributional shape of the continuous variables (i.e., age, weight, total thiopentone dose, duration of anesthesia, length of incision, maximal pain score). One-way analysis of variance (ANOVA) was used to detect differences among the groups. Cross tabulation with chi-square tests and Monte Carlo significance was used to measure associations among the categorical variables (i.e., breed, sex, type of surgery, and sedation score). Values of P ≤0.05 were considered statistically significant. All statistical analyses were performed with SPSS 14.0 for Windows software.j Descriptive statistics are expressed as mean ± standard deviation (range).
Results
Sixty dogs (35 females, 25 males) of various breeds [Table 1] undergoing a wide range of surgeries [Table 2] were included in the study. The average age of the dogs was 4.9±2.9 (1 to 10) years, and the average weight was 18.5±9.8 (4.5 to 50) kg. The average total dose of thiopentone was 8.7±1.9 (6 to 12.5) mg/kg, and the average duration of anesthesia was 92±27 (45 to 172) minutes. The average incision length was 7.5±2.2 (5 to 10.5) cm. All continuous variables tested as normally distributed.
The age, weight, and maximal pain scores for the four groups are shown in Table 3. The four groups were homogenous with respect to age (P=0.474), weight (P=0.221), breed (P=0.542), sex (P=0.680), type of surgery (P=0.823), duration of anesthesia (P=0.357), ASA physical status (P=0.550), total thiopentone dose (P=0.721), and incision length (P=0.277). No dog required additional analgesia during anesthesia.
Pain scores peaked within 2 hours after surgery in 48 of 60 dogs, within 3 hours in 55 of 60 dogs, and within 4 hours in all dogs. Seven dogs were fully alert (sedation score 0) by the first hour after surgery; 47 of 60 dogs were fully alert by the second hour; and all dogs were fully alert by the third hour. Supplemental postoperative analgesia was given to none of the 15 dogs in group B-pre, seven of the dogs in group B-post, 11 of the dogs in group NS-pre, and 11 of the dogs in group NS-post. The mean maximal pain score in group B-pre (3.67) was significantly lower than those in groups B-post (5.60, P=0.001), NS-pre (6.67, P<0.0005), or NS-post (6.53, P<0.0005). Differences between the other pairs were not significant [Table 4]. Group B-pre was also associated with less frequent use of additional postoperative analgesia compared with use in the other three groups (P<0.0005). No association was found between the sedation scores and the groups in the first (P=0.355) and second (P=0.644) hour postoperatively.
Discussion
Pain after abdominal surgery is a multifactorial process that includes somatic pain (from the distention of the peritoneum, tearing of blood vessels, traction of nerves, and release of inflammatory mediators) as well as visceral pain. Therefore, a preemptive, multimodal approach is needed to manage postoperative pain; this may include blockade of peripheral nociceptors along with administration of centrally acting analgesics. Furthermore, surgery may induce a stress response along with associated changes in metabolism and neuroendocrine function. Stress can induce complement activation and cause the release of cytokines, arachidonic acid metabolites, nitric oxide, and oxygen-free radicals, which may in turn lead to subsequent organ failure and morbidity.14,23,27,28 Activation of the peripheral and central nervous systems plays a major role in nociception and the metabolic and hormonal responses associated with surgical stress.
To be most effective, preemptive analgesia must prevent transfer of noxious stimuli to the central nervous system, while also reducing or eliminating peripheral inflammation. Peripheral inflammation augments input to the central nervous system, thus aggravating central hypersensitivity.1
The major mechanism of action of local anesthetics is the stabilization of peripheral nerve membranes. However, local anesthetics affect many membrane-associated proteins in tissue and can inhibit the release and action of agents like prostaglandins and lysosomal enzymes, which sensitize or stimulate nociceptors and promote inflammation.29 In people, peripheral neural blockade with local anesthetics seems to be the best technique to reduce the surgical stress response.28 These same effects have also been shown in a swine model.23
In the authors’ study, preoperative infiltration of bupivacaine at the incision site significantly reduced postoperative pain in dogs after celiotomy. This reduction was also accompanied by a significant reduction in the number of dogs requiring additional postoperative analgesia. In fact, no opioids were required at all in the B-pre group. In contrast, postoperative infiltration with bupivacaine did not achieve an acceptable degree of analgesia, so the postoperative administration of opioids was required in a significantly greater number of dogs in this group than in group B-pre. The authors conclude that preoperative incisional block with bupivacaine provides effective preemptive analgesia in dogs after celiotomy. This analgesic effect lasted for at least 24 hours, which is much longer than the 6- to 12- hour duration of action reported for bupivacaine.1,30 This suggests a preemptive effect of bupivacaine, because analgesia only from peripheral neural blockade should have lasted no more than 12 hours postinfiltration. Worth noting, however, is the fact that rebound-type pain has still been reported in human patients in whom bupivacaine was infiltrated into the surgical wound.32
The authors selected bupivacaine because of its long duration of action, which reduces the risk of central sensitization after premature cessation of action during the postoperative period. Other local anesthetics with a shorter duration of action (e.g., lidocaine) could have been combined with epinephrine to prolong the effect, but the vasoconstriction associated with epinephrine has been shown to impair wound healing.31
The authors deliberately selected a general anesthetic protocol that is associated with relatively short-acting analgesia. Meperidine was chosen for its short duration of intraoperative analgesia, so that bupivacaine would be the only analgesic drug acting postoperatively. No NSAIDs were used for the same reason. A placebo-controlled design was chosen to increase the strength of the trial. However, accurate and reliable systems for scoring pain should make it possible to devise a humane study that includes an untreated group, but with intervention therapy if the pain score increases above a predefined threshold.25 No dog in this study was left unattended during the trial, and signs of pain or discomfort were treated immediately whenever noted.
Objective measures such as heart rate, respiratory rate, and temperature are unreliable estimates of pain, as are humoral factors such as adrenaline, noradrenaline, cortisol, β-endorphins, and free fatty acids. The baseline concentrations of these substances vary widely among individuals, making interpretation of results difficult. Therefore, all scoring systems for pain rely primarily on behavioral signs.25,26 The authors used a numerical rating scale that has been judged suitable for assessing pain in a clinical setting, assuming a single knowledgeable person is responsible for perioperative pain management.25
Pain assessment may prove difficult in tranquilized or heavily sedated animals, because residual sedation from sedatives, anesthetics, and/or analgesic drugs may mask pain behavior.26 In this study, maximal pain scores were recorded in 48 of 60 dogs within 2 hours. Minimal sedation was noted in 47 of 60 dogs during this same 2-hour period, with all dogs fully aware within 3 hours after surgery. Furthermore, bupivacaine has no marked sedative effects, and the analgesic premedicants that were administered were not expected to last for a long time after surgery. Thus, pain assessment was not likely affected by residual sedation.
Achieving even distribution of local anesthetic into the tissues of a surgical site can sometimes be technically difficult and often result in “patchy” analgesia;1,33 therefore, care should be taken to infiltrate each tissue plane within a surgical site so as to provide effective analgesia. The authors used a low concentration (0.25%) of bupivacaine so that a relatively large volume of analgesic fluid could be distributed evenly into the surgical tissues. Infiltration of large volumes of local anesthetic may increase the risk of systemic absorption and side effects in people,34 but this was not a major concern in this study. The 2 mg/kg dosage that was administered is less than the maximal safe dosage for most species (i.e., 2.2 mg/kg in small animals)30 and only half the toxic dosage (4 mg/kg).1 Moreover, similar dose and volume rates of lidocaine infiltration have been shown to be safe in dogs.35 Large volumes of fluid have been suggested to possibly adversely affect wound healing, 36 but infiltration of local anesthetics does not appear to significantly delay wound healing in animals.1
Local anesthetics should contact the tissues for at least 20 minutes for best effect.30 In group B-pre, the authors administered bupivacaine just before making the skin incision. Therefore, they hypothesize that even lower pain scores could have been achieved in this group if a reasonable amount of time had been allowed to elapse between infiltrating the wound and incising the skin to achieve maximal bupivacaine effect. Such a delay, however, may have interfered with scheduled surgery times and increased anesthesia duration. Furthermore, the authors also felt that the study protocol should resemble the norm in general practice as closely as possible. In the future, more flexible perioperative management incorporating earlier bupivacaine administration may be indicated for routine surgeries.
In people, clinical trials investigating the effectiveness of preoperative wound infiltration on postceliotomy pain relief have had controversial results. Suggested reasons for this inconsistency include the fact that somatic afferents have a greater effect on stress and postoperative pain than visceral afferents.37 However, it should be remembered that peripheral nociception is only one of the components involved in postoperative pain. Other components may include visceroperitoneal nociception (e.g., from visceral manipulations and inflammation), rhinogastric and urethral catheterization, and psychological stress.38,39
Studies have suggested that pain arising from viscera and deeper peritoneal layers may be of greater significance than pain from cutaneous, subcutaneous, and muscular layers of an incision. Therefore, afferents from deeper structures would be unaffected by wound infiltration.19 Indeed, studies in people have shown that wound infiltration with local anesthetic is more effective in minor surgeries than in major ones.39
In veterinary medicine, preoperative incisional block seems to produce adequate postoperative analgesia after celiotomy,22,23 which is in contrast to the inconsistent results reported in human medicine. This apparent contradiction may suggest that celiotomies cause less postoperative pain in small animals, probably because quadrupeds use less of the abdominal muscles during walking and breathing than people do.41 The inconsistent results from human medicine may also be caused by the different surgical techniques used in various trials (e.g., midline, flank, or transverse incisions15–21), preventing results from being directly comparable. Interestingly, evidence has shown that wound tenderness in cats is greater after a flank approach for ovariohysterectomy than after a midline incision. 40 In addition, inconsistent results from human trials may be related to poor clarification of the term “wound infiltration,” which may have been used to describe both subcutaneous (only) and full-thickness infiltration of the surgical incision.18
Conclusion
Preoperative wound infiltration with bupivacaine is a simple, attractive, and effective technique to reduce postoperative pain for at least 24 hours after celiotomy in dogs. Further studies are needed to investigate its application to other types of surgery.
Calmivet, Vetoquinol; Lure Cedex, 70204, France
Pethidine hydrochloride; Famar, Athens, GR-17456, Greece
Pentothal, Abbott Laboratories Hellas, Athens, GR-17456, Greece
AErrane; Baxter Healthcare Ltd., Norfolk, IP243SE, United Kingdom
PC Scout; SpaceLabs Medical Inc., Redmond, WA 98073–9713
Capnomac Ultima; Datex-Engstrom, Helsinki, FIN-00101, Finland
Bupivacaine; Laboratoire Aguettant, Lyon, 69007, France
Fentanyl; Janssen Pharmaceutica NV, Beerse, B-2340, Belgium
Morphine hydrochloride; Demo, Athens, GR-14568, Greece
SPSS 15.0; SPSS Inc., Chicago, IL 60606–6412
