Recipient Organization
UNIV OF PENNSYLVANIA
(N/A)
PHILADELPHIA,PA 19104
Performing Department
CLINICAL STUDIES
Non Technical Summary
Colic is reported as the most prevalent equine emergency and may require surgical intervention depending on the underlying lesion. With strangulating small intestinal lesions, resection of nonviable bowel is necessary, and can take considerable time to perform. Expedient correction of the lesion and steps to reduce total surgery and anesthesia time are considered goals for any surgeon as anesthetic events such as hypoxemia and hypotension that frequently occur in horses undergoing colic surgery, can contribute to post-operative morbidity and mortality. Small intestinal disease represents about 25-64% of colic cases where 60-80% have a strangulating lesion often requiring resection and anastomosis (Freeman, 1999). Ligation of the vascular arcades associated with segments of bowel to be resected is an essential initial step in performing resection and anastomosis of the bowel. With long segments, this can take considerable time to perform adding to the total surgical time. Use of hemostatic clips, electrothermal coagulation and sutured ligations are considered mainstays for achieving mesenteric vascular occlusion and hemostasis. Disadvantages of handsewn ligation can be slippage and increased operative time. Disadvantages of electrothermal coagulation include expense of the equipment and limited vessel size (£7mm) sealing ability (Rumbaugh et al, 2003). Recently, the LDS (Autosure LDS 15W; Ligate Divide and Staple) an automated device became unavailable to purchase and use as the manufacturer discontinued its production. The LDS was an attractive alternative to handsewn ligations in colic surgery as it reliably discharged two hemostatic clips and cut between the two, making mesenteric vessel ligation fast. Nowadays, surgeons typically perform two or three encircling suture ligations per arcade or may use an electrothermal coagulation and fusion device (LigaSure®) in combination with sutured ligations. As such, we believe there is a need to find an alternative method for vessel ligation that is safe, effective, fast and ideally inexpensive.Cable ties (CT) have been used in veterinary medicine for a variety of applications including colonic vascular ligation in horses (personal communication and experience), neonatal foal rib stabilization (Williams et al, 2017; Downs and Rodgerson, 2011), ovariohysterectomy in cats (Zagranski, 1980), splenectomy in cats (Zagranski, 1979) and rhesus monkey (Adams and Narayan, 1993), nephrectomy in pigs (Hoglund et al, 2011) and ovarian vascular pedicles in mares (Cokelaere et al, 2005).We believe that nylon CT (NCT) may be a useful alternative to handsewn ligation for fast and safe mesenteric vessel ligation in horses undergoing jejunal resection and anastomosis. Based on previous studies in animals, there is both experimental and clinical support for the use of a cable tie construct for vessel occlusion in colic surgery in horses. Furthermore, omentectomy is a recognized technique to reduce post-operative adhesion development in horses (Kuelbelbeck et al, 1998). We propose that NCT can be used to ligate the greater omentum without significant hemorrhagic complication.Resection and anastomosis of the small intestine continues to be associated with high complications (50-64%) and lower than optimal survival rates (76-88%) (Morton and Blikslager, 2002; Mair and Smith, 2005). Choosing a technique that is watertight, minimizes luminal reduction, and is faster to perform is ideal to minimize surgery and anesthesia times. Handsewn end to end anastomoses can be performed in 1 or 2 layers, with continuous or interrupted and appositional or inverting techniques. A 2 layer technique using continuous appositional mucosa/submucosal closure followed by either continuous appositional or inverting seromuscular closure is most commonly performed. Single layer techniques using a continuous Lembert pattern have been evaluated in vivo (Mendez-Angulo et al, 2010; Close et al, 2014) as safe and technically faster to perform than 2 layer techniques. Ex vivo assessment of a 1 layer continuous Cushing pattern was also shown to be similar to 1 layer Lembert or 2 layer technique regarding bursting pressure, and lumen size reduction, but are yet to be evaluated in vivo. Further, 1 layer techniques are faster to perform than 2 layer (Sherlock et al, 2011)Safe performance of surgical procedures on horses in lateral or dorsal recumbency requires general anesthesia, a procedure unfortunately associated with a high mortality rate (Dugdale & Taylor 2016). Peri-anesthetic mortality is due, in part, to pulmonary pathophysiologic features arising from hypoxemia and hypotension that can occur during prolonged periods of recumbency. While controlled ventilation techniques to keep the lungs ventilated have been developed to reduce such complications, the large weight of the abdominal viscera of the horse that lies directly on the diaphragm during dorsal recumbency (Hedenstierna et al. 2005) increases the risk of hypoxia resulting from compression atelectasis in non-aerated lung areas (Nyman et al. 1990; Sorenson & Robinson 1980). In addition, the lower lung fields - that are preferentially perfused during dorsal recumbency - are also the most affected by the abdominal pressure and therefore have the highest risk for collapse (Stack et al. 2014). As intraoperative hypoxemia and lung-collapse are associated with prolonged intensive care unit and hospital stays due to increased rates of respiratory failure and pneumonia (Shander et al. 2011; Tusman et al. 2012), ventilation strategies that improve oxygenation in horses undergoing general anesthesia are required to reduce intra- and postoperative complications.Traditionally, mechanical ventilation is achieved via active lung inflation during inspiration and passive lung emptying during expiration. Multiple studies, including our own, have shown that high inspiratory pressures followed by sustained positive end-expiratory pressures (PEEP) can improve gas exchange in anesthetized patients (Hopster et al. 2011; Hopster et al. 2016; Hopster et al. 2017; Wettstein et al. 2006). However, positive pressure provided during mechanical ventilation can cause ventilator?induced lung injury even in healthy subjects as a consequence of an imbalance between lung stress and strain (Kuchnicka et al. 2013). In addition, excessive PEEP can impair cardiovascular function by compressing the vena cava and reducing venous return to the heart, leading to reduced stroke volume and cardiac output (Hopster et al. 2017), clearly undesirable outcomes.Currently, the expiration phase in nearly all mechanical ventilation modes is passive and therefore governed by the mechanical characteristics of the respiratory system. However, prolonging the expiration phase represents a potentially powerful and innovative way to improve oxygenation. Indeed, the FLow-controlled EXpiration (FLEX) mode was recently introduced as an approach to lung-protective ventilation (Schumann et al. 2014; Goebel et al. 2014). FLEX modulates the otherwise passive expiration phase: reducing the initial high-expiratory peak flow and causing expiratory gas flow to persist throughout the expiratory phase. In studies of human patients, FLEX increased ventilation in the dorsal-dependent lung regions, thereby homogenizing the ventilation distribution (Wirth et al. 2017) and improving the distribution of gas flow and ventilation at the consecutive breath. Moreover, in an animal model of acute respiratory distress syndrome, FLEX reduced ventilation-induced lung damage, decreased severity of pulmonary edema and focal inflammation, increased dynamic compliance, and improved ventilation. (Goebel et al. 2014). Notably, FLEX ventilation is predicted to be even more beneficial for patients with large body mass, as their expiration is relatively rapid compared with that in patients with high compliance or lower body mass (Tremblay and Slutsky 2006).
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Goals / Objectives
We hypothesize that nylon cable ties will be a simple, fast, effective and safe method of jejunal mesenteric vessel ligation compared to handsewn jejunal mesenteric vessel ligation. Further, we hypothesize that a 1 layer continuous Utrecht jejunojejunostomy will be faster, be as safe and have no increased incidence of anastomotic morbidity in vivo compared to a 2 layer appositional jejunojejunostomy.Objective(s): We will investigate the safety, efficacy and impact on surgery time of using NCT for jejunal mesenteric ligation compared to convention hand sewn ligation.We will investigate the safety, incidence of morbidity and surgical times of performing a single layer Utrecht jejunojejunostomy compared to 2 layer appositional jejunojejunostomy.The aim of this study is to test the FLEX-ventilation mode during anesthesia in horses. We hypothesized that this ventilation mode can be used for intraoperative ventilation having positive effects on respiratory system mechanics, gas exchange, and no negative effects on the cardiovascular system.Objective: We will investigate respiratory system compliance, arterial oxygenation, and hemodynamics in healthy horses ventilated with and without FLEX.
Project Methods
Anesthesia and ventilationAnesthesiaHorses will be anesthetized twice with a washout period of 2 weeks.A 14-gauge catheter will be aseptically placed in the left jugular vein. Horses will be pre-medicated with 0.8 mg/kg xylazine IV and induced with 0.05 mg/kg midazolam and 2.2 mg/kg ketamine IV. After induction, orotracheal intubation will be performed prior to positioning of the animal. The animals will be placed in dorsal recumbency on a thick, foam pad. Following induction and positioning the animals will be connected to a large animal rebreathing circuit and a volume-controlled ventilation mode will be initiated using an anesthesia workstation.Anesthesia will be maintained with isoflurane at an end tidal concentration of 1.3 to 1.5% in pure oxygen. Intravenous crystalloid solution will be administered at a rate of 5ml/kg/hr for the duration of the procedure. Blood pressure support will be provided by administration of dobutamine as a continuous rate infusion as needed to maintain a mean arterial blood pressure (MAP) above 70mmHg. A 20-gauge catheter placed in the facial artery will allow for invasive blood pressure monitoring and arterial blood sampling.Following completion of data collection, the horses will be hoisted off the mattress and moved to a separate recovery stall. The orotracheal tube will be removed and replaced by a nasotracheal tube. Supplemental oxygen will be provided by oxygen demand valve until spontaneous ventilation resumes. At this time, 0.2 mg/kg xylazine will be administered and horses allowed to free recover.Ventilation strategyHorses will be ventilated immediately after induction of anesthesia. Tidal volume will be set to 14 mL/kg throughout the experiment, while respiratory rate was adjusted to maintain an end-tidal CO2 tension of 35-40 mmHg.Respiratory gas volumes, airway pressures and the dynamic compliance (Cdyn) will be measured using a Pitot-based flow meter which will be calibrated with a three-liter calibration syringe before every experiment. Arterial blood samples will be taken, and an arterial blood gas analysis will be performed to measure the arterial oxygen partial pressure (PaO2). Measurements will be performed every 15 minutes.OmentectomyDay 1 - First anesthetic eventHorses will be prepared for aseptic celiotomy and a 30-cm ventral midline incision will be made (HAR). The greater omentum will be identified and exteriorized. A single sterilized (ethylene oxide gas) nylon cable tie (NCT; 0.9 x 45.7cm band length and 7 x 12mm locking case) will be placed around the entire omentum as proximal toward the stomach as possible. The NCT will be pulled tightly until it is unable to be closed (HAR and SH). The excessive band length will be cut to a length of < 5mm. An Ochsner clamp will be placed on the omental pedicle. The omentum will then be transected using straight Mayo scissors 5mm distal from the NCT. Visual assessment of hemorrhage will be made. If none, the omental pedicle will be release. If hemorrhage is noted, transfixation sutures using 0 polyglactin 910 will be performed (rescue procedure; SH). The time take from placement of the NCT to transection of the omentum will be recorded.Day 15 - Second anesthetic eventHorses will be prepared for aseptic celiotomy and a 30-cm ventral midline incision will be made (HAR). The omentectomy site will be visually assessed for presence of tissue reaction, adhesions etc. The NCT and omental stump will be identified, excised and placed in 10% buffered formalin (HAR/SH).Jejunal Vessel LigationDay 1 - First anesthetic eventAn approximately 10-feet section of mid jejunum will be identified for proposed resection and anastomosis (see part 3). The vascular arcades will be assessed for optimal sites for R&A. The number of vascular arcades in the proposed R&A site will be recorded. Two 5mm fenestrations will be made in the mesentery approximately 15 cm away from the intestinal border to allow placement of a sterilized NCT (identical dimensions per omentectomy) around the entire mesenteric segment to be ligated. The NCT will be pulled tightly until it is unable to be closed (SH). A second NCT will be placed in identical fashion 5mm distal to the first. The entire mesentery will be transected 5mm distal to the second NCT using straight Mayo scissors. Visual assessment for hemorrhage will be made. If present, hand sewn ligatures using 2-0 Polyglactin 910 will be placed (rescue procedure; SH). The time taken to perform mesenteric ligation from initial NCT placement to transection will be recorded.Day 15 - Second anesthetic eventHorses will be prepared for aseptic celiotomy and a 30-cm ventral midline incision will be made (HAR). The NCT mesenteric ligation site will be visually assessed for presence of tissue reaction, adhesions etc.An approximately 10-feet section of mid-distal jejunum will be identified for proposed resection and anastomosis (see part 3). The vascular arcades will be assessed for optimal sites for R&A. The number of vascular arcades in the proposed R&A site will be recorded. Mesenteric vessel ligation will be performed by placed 2 encircling ligatures using 2-0 Polyglactin 910 around each vessel. The total time taken to ligate each vessel for the proposed R&A will be recorded (SH).After a second jejunojejunostomy is performed (see part 3), horses will be euthanized under anesthesia. The NCT mesenteric ligation site (from day 1) will be excised and placed in 10% buffered formalin (HAR/SH).Jejunojejunostomy Day 1- First anesthetic eventFollowing parts 1 and 2 aforementioned, an end-to-end jejunojejunostomy will be performed in either 1 layer (1JJ) or 2 layers (2JJ). Horses will be randomly assigned by giving them a number then using a random number generator will determine the anastomosis pattern performed at the first surgery.The small bowel will be manually decompressed into the cecum. Penrose drains will be placed oral and distal to the proposed R&A. Either a single layer, seromuscular, continuous Utrecht anastomosis (1JJ) or a two layer, simple continuous mucosa/submucosa then simple continuous seromuscular anastomosis (2JJ) will be performed. Polydioxanone (PDS II) size 2-0 will be used for all anastomoses. The time taken from the placement of the first suture to the end of tying of the last knot will be recorded. Penrose drains will be removed, and all mesenteric defects will be closed using 2-0 polyglactin 910. Each anastomosis will be leak tested before returning the bowel to the abdomen (SH).Day 15- Second anesthetic eventHorses will be prepared for aseptic celiotomy and a 30-cm ventral midline incision will be made (HAR). The R&A site will be visually assessed for presence of tissue reaction, adhesions etc.Following mesenteric vessel ligation (see part 2), a second jejunojejunostomy will be performed. If a horse had a 1JJ performed at the first surgery, a 2JJ will be performed at the second and vice versa. The total construct time will be recorded as before (SH). Following the R&A, horses will be euthanized under anesthesia. The R&A sites from the first surgery (i.e. following 14 days of healing) will be harvested and placed in 10% buffered formalin.