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surgical manipulation (Southwood 2019). To reduce the risk of tearing the colon wall during attempts to correct a nephrosplenic entrapment, intraoperative use of phenylephrine has been recommended (Hardy et al. 2000). Phenylephrine is a sympathomimetic amine that acts predominantly on alpha-1 adrenergic receptors to induce peripheral vasoconstriction and splenic contraction. Adverse cardiovascular effects associated with intravenous phenylephrine administration under general anaesthesia have been reported; these include a significant decrease in cardiac output, heart rate, gastrointestinal blood flow and peripheral tissue oxygenation (Ohta et al. 2013; Dancker et al. 2018). The half-life of phenylephrine is unknown in horses, though in human subjects it is approximately 2–3h, and the cardiovascular effects last for a longer period (Ohta et al. 2013). Therefore, using sequential doses in close succession should probably be avoided whenever possible. Intravenous administration of phenylephrine has also been associated with fatal bleeding disorders, particularly in horses older than 15 years (Frederick et al. 2010; Compostella et al. 2012). It has been hypothesised that older horses have reduced vessel compliance and altered vessel elasticity, making them more susceptible to damage secondary to phenylephrine-induced vasoconstriction and secondary hypertension (Frederick et al. 2010). It is advisable to administer phenylephrine slowly over a period of 15 min or potentially longer to avoid excessive vasoconstriction due to the rapid increase in plasma concentration, which may predispose to haemorrhage. Doses associated with haemorrhage in the series of cases reported by Frederick et al. (2010) ranged from 10 to 30 mg given in saline over 15 min. Three out of the five reported cases of haemorrhage occurred immediately after administration of phenylephrine and without any period of forced exercise. Administration of phenylephrine intravenously at a dose of
3 lg/kg bwt/min over 15 min to normal horses can decrease normal splenic area by 28% (Hardy et al. 1994). This reduction in splenic size persists for 15–20 min after infusion and can facilitate repositioning of the colon during surgical correction of nephrosplenic entrapment (Hardy et al. 1994). Conflicting opinions exist regarding the efficacy of intravenous phenylephrine use. Hardy et al. (1994) showed a significant increase in resolution of nephrosplenic entrapment after intravenous administration of 3 lg/kg bwt/min phenylephrine for 15 min in combination with rolling or exercise, compared with horses that were not given phenylephrine. Baker et al. (2011) did not find a significant effect of administration of phenylephrine at the same dose when used in combination with rolling in 71 horses, compared with 16 horses not administered phenylephrine. The case report by Loomes and Anderson (2020) presents another example of intravenous phenylephrine not being particularly helpful in combination with exercise, nor in subsequent attempts to correct a nephrosplenic entrapment during exploratory laparotomy. The authors hypothesised that the entrapped large colon may have obstructed the splenic vasculature, preventing splenic contraction in response to intravenous phenylephrine administration. Lack of response to intravenous phenylephrine may be encountered in patients suffering severe sepsis or septic shock. Low vascular reactivity to vasopressors is linked to desensitisation or down-regulation of alpha-1 adrenergic receptors in response to massive release of endogenous catecholamines (Benedict and Rose 1992). However,
nephrosplenic entrapment is typically a non-strangulating lesion and it would be uncommon for a horse with such a displacement to present with severe sepsis. Another factor to consider is that studies reporting the degree of splenic contraction in response to phenylephrine administered intravenously were performed in normal horses. In a clinical case, partial obstruction of the blood supply within the hilus of the spleen by a heavy displaced colon, and other cardiovascular derangements related to hypovolemia and stress may result in a lack of response. In the case report by Loomes and Anderson (2020), a 10 mg dose of phenylephrine was administered directly into the spleen, following unsuccessful attempts to correct nephrosplenic entrapment after administering intravenous phenylephrine
and emptying the colon as much as possible via pelvic flexure enterotomy. In this case, direct administration of phenylephrine into the spleen resulted in appreciable splenic contraction allowing the displacement to be corrected, presumably due to a high local concentration of phenylephrine. It is unknown whether intra-splenic injection of phenylephrine would have been effective without first performing a large colon enterotomy. Intra-splenic injection of 10 mg phenylephrine resulted in a 15% higher mean arterial blood pressure peak than the previous intravenous dose of 24 mg, probably due to rapid ejection of stored splenic blood into the systemic vasculature with subsequent generalised alpha-1 receptor agonism. It is possible that lower doses of phenylephrine injected directly into the spleen may be efficacious, resulting in fewer systemic cardiovascular side effects. Further studies are indicated to determine the lowest local dose that will induce splenic contraction, identify any unexpected adverse effects of intrasplenic phenylephrine injection, and to compare the effect of intravenous vs. intrasplenic injection of phenylephrine on cardiac output and splanchnic perfusion in equine cases. Recurrence of left dorsal displacement of the large
colon or nephrosplenic entrapment is reported in up to 8%– 23% of horses (Hardy et al. 2000; Nelson et al. 2016).
Nephrosplenic space ablation may be performed via left flank laparotomy or a laparoscopic approach to reduce the risk of re-entrapment. The nephrosplenic space is closed by either suturing the nephrosplenic fascia/ligament to the dorsomedial splenic capsule, or via mesh ablation (Farstvedt and Hendrickson 2005; Epstein and Parente 2006). Inducing splenic contraction via intravenous administration of sympathomimetic drugs is reportedly helpful in the suturing procedure. It is possible that a greater degree of splenic contraction may be achieved by injecting phenylephrine locally, as described by Loomes and Anderson (2020), however, further experimental work is needed. It is important to inform owners that nephrosplenic space closure does not prevent other types of displacement of the large colon, including left dorsal displacement without entrapment in the nephrosplenic space. Colopexy is another option to prevent left dorsal displacement but is not recommended for athletic horses, and displacement of the large colon around the colopexy may still occur (Hunt and Spirito 1995). Horses are unlikely to re-entrap or displace the large colon following large colon resection (depending on how much of the colon is removed), however the procedure is more invasive, and some horses may require dietary modification at least in the short term post-operatively (Bertone et al. 1989).
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