A hemostatic spray: the easy way out for upper gastrointestinal bleeding?

It is now generally accepted that early endoscopic intervention (i. e. within 24 hours after admission) improves outcomes in patients who present with a significant upper gastrointestinal bleed [1] [2]. Several techniques are available to achieve hemostasis during endoscopy. Injection therapy with diluted epinephrine is cheap and relatively easy to perform but should no longer be used as a monotherapy [3]. Injection therapy should be combined with other techniques, amongst which coaptive coagulation (a combination of pressure and thermal therapy) and application of hemoclips appear to be more or less equally effective.

Endotherapy for upper gastrointestinal bleeding can be challenging. First, bleeding may occur from sites that are difficult to approach, such as the posterior duodenal wall or the upper region of the lesser gastric curvature,and this may make it hard to place hemoclips or apply adequate pressure with coagulation probes. Secondly, upper gastrointestinal bleeding can be a life-threatening situation that often presents outside normal working hours. Murphy’s law has it that the most severe and difficult bleedings occur preferentially during those nights that the least skilled endoscopist is on call, assisted by the youngest nurse of the team. In this issue of Endoscopy, two papers report on an exciting new endoscopic hemostatic technique that may allow effective endoscopic therapy under these circumstances. In both studies, Hemospray was utilized to control upper gastrointestinal bleeding, the substance being delivered in short bursts under pressure, by means of a small handheld canister of carbon dioxide and a spray catheter positioned at 1 – 2 cm from the bleeding artery. The material used for this technique is a proprietary inorganic powder. In the military setting, topical granular hemostats have been used on the battlefield to control bleeding for many years with great success, particularly in irregularly shaped wounds [4] [5]. When spray is applied, it leads to the formation of a stable mechanical barrier that adheres to and covers the bleeding site.

Giday et al. [6] induced severe gastric arterial bleedings in pigs by first surgically transposing a branch of the gastroepiploic artery in the gastric lumen followed by endoscopic transection of the vessel using a needle knife, consequently inducing a severe spurting arterial bleeding. To complicate matters further, all animals were heparinized to therapeutic levels. Animals were randomized to either observation or application of TC-352 (Hemospray). Whereas all untreated animals succumbed, acute hemostasis was achieved in all five treated animals. In only one animal there was evidence of rebleeding, with blood being seen in the stomach during endoscopy 24 hours after treatment although no active bleeding was found. Based on this promising animal work a clinical study was conducted: Sung et al. [7] used the Hemospray in 20 patients with active peptic ulcer bleeding and achieved immediate cessation of the bleeding in 95 %; the single patient in whom Hemospray failed had a bleeding pseudoaneurysm that was effectively embolized during angiography, but other endoscopic measures would likely also have failed in this case. After 3 days, Hemospray was found to be eliminated from the stomach and duodenum in all patients. No adverse effects were noted, related either to bowel obstruction (which might have been anticipated when the Hemospray layer sloughed off), or embolus formation caused by particles entering the bloodstream on account of the pressured delivery mechanism.

The results of both studies are quite spectacular and hold the promise of a real breakthrough in the treatment of upper gastrointestinal bleeding. The technique appears surprisingly simple and should require a lower level of endoscopic skills than coagulation or clipping. The reported studies, however, do have some weaknesses. Obviously, the arterial bleedings caused in the animal model are artificial and differ from real-life peptic ulcer bleeding. One might speculate that the fibrosis at the base of a peptic ulcer might inhibit the retraction and vasoconstriction of the bleeding artery, resulting in a higher rate of rebleeding after initial hemostasis. In the human study, only relatively mild bleedings were treated (95 % had Forrest-type Ib lesions, i. e., oozing bleeding), and patients with hemodynamic instability were excluded. Several issues thus remain to be investigated: will the Hemospray perform just as well for more severe bleedings? How long is the coagulum maintained on the ulcer base? What are the effects of the Hemospray on wound healing? Are there side-effects related to applying Hemospray too aggressively?

Nevertheless, these initial reports are very promising, and it is tempting to speculate about the potential role of this fascinating new treatment modality. Will Hemospray obviate the need for additional endoscopic treatment: will simply spraying the material on a spurting vessel suffice as a definitive therapy? That sounds almost too good to be true. Or will this technique be used as a temporary measure, stopping severe bleedings in an effective and simple manner, even in situations where Murphy’s law appears to apply, so we can wait till the following day to have a more experienced colleague apply the final treatment under optimal circumstances? One might also speculate that the Hemospray might be an effective temporary measure during the initial endoscopic procedure, since the material that is not integrated into the bleeding site can be easily washed away. This would facilitate immediate application of a more permanent hemostatic technique during the same treatment session. Ongoing studies will likely address these issues.

The use of the Hemospray has so far been restricted to ulcer bleedings. What about that other night-disturbing cause of severe upper gastrointestinal bleeding: variceal bleeding? Will more or less blind spraying of the material into a blood-filled distal esophagus or gastric fundus stop these bleedings too? In variceal bleeding the risk of the material entering the bloodstream, with the potential risk of embolus formation, might be higher than in arterial bleeding. This is surely a potential application that warrants further animal studies.

This Hemospray device is not yet commercially available and has regulatory clearance in only Canada and Hong Kong. For the time being we will therefore still have to rely on our endoscopic skills and current hemostatic techniques to appropriately treat our bleeding patients. For those of us who sometimes struggle with these cases (and who does not?) it is nice to know that a promising new tool may soon become available.

References

• 1 Cook D J, Guvatt G H, Salena B J, Laine L A. Endoscopic therapy for nonvariceal uppergastrointestinal hemorrhage: a meta-analysis.  Gastroenterology. 1992;  102 139-148
• 2 Barkun A, Bardou M, Marshall J K et al. Consensus recommendations for managing patientswith nonvariceal upper gastrointestinal bleeding.  Ann Intern Med. 2003;  139 843-857
• 3 Sung J J, Kelvin K K, Lai L H et al. Endoscopic clipping versus injection and thermo-coagulation in the treatment of non-variceal upper gastrointestinal bleeding: a meta-analysis.  Gut. 2007;  56 1364-1373
• 4 Alam H B, Burris D, DaCorta J A, Rhee P. Hemorrhage control in the battlefield: role of newhemostatic agents.  Mil Med. 2005;  170 63-69
• 5 Pozza M, Millner R W. Celox (chitosan) for haemostasis in massive traumatic bleeding:experience in Afganistan.  Eur J Emerg Med. 2011;  18 31-33
• 6 Giday S A, Kim Y, Krishnamurty D M et al. Long-term randomized controlled trial of a novel nanopowder hemostatic agent (TC-325) for control of severe arterial upper gastrointestinal bleeding in a porcine model.  Endoscopy. 2011;  43 295-208
• 7 Sung J JY, Luo D, Wu J CY et al. Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding.  Endoscopy. 2011;  43 290-294