Using naso- and oro-intestinal catheters in physiological research for intestinal delivery and sampling in vivo: practical and technical aspects to be considered

Abstract

Intestinal catheters have been used for decades in human nutrition, physiology, pharmacokinetics, and gut microbiome research, facilitating the delivery of compounds directly into the intestinal lumen or the aspiration of intestinal fluids in human subjects. Such research provides insights about (local) dynamic metabolic and other intestinal luminal processes, but working with catheters might pose challenges to biomedical researchers and clinicians. Here, we provide an overview of practical and technical aspects of applying naso- and oro-intestinal catheters for delivery of compounds and sampling luminal fluids from the jejunum, ileum, and colon in vivo. The recent literature was extensively reviewed, and combined with experiences and insights we gained through our own clinical trials. We included 60 studies that involved a total of 720 healthy subjects and 42 patients. Most of the studies investigated multiple intestinal regions (24 studies), followed by studies investigating only the jejunum (21 studies), ileum (13 studies), or colon (2 studies). The ileum and colon used to be relatively inaccessible regions in vivo. Custom-made state-of-the-art catheters are available with numerous options for the design, such as multiple lumina, side holes, and inflatable balloons for catheter progression or isolation of intestinal segments. These allow for multiple controlled sampling and compound delivery options in different intestinal regions. Intestinal catheters were often used for delivery (23 studies), sampling (10 studies), or both (27 studies). Sampling speed decreased with increasing distance from the sampling syringe to the specific intestinal segment (i.e., speed highest in duodenum, lowest in ileum/colon). No serious adverse events were reported in the literature, and a dropout rate of around 10% was found for these types of studies. This review is highly relevant for researchers who are active in various research areas and want to expand their research with the use of intestinal catheters in humans in vivo.

Keywords: aspiration; colon; delivery; human; ileum; intestinal catheter; small intestine; trials.

FIGURE 1

Flowchart of the literature search for articles that used an intestinal catheter where the tip was in the jejunum, ileum, or colon for research purposes in human subjects. Searches were performed up to 16 March 2020.

FIGURE 2

An overview of the general characteristics of the 60 studies included that used an oro- or naso-intestinal catheter placed in the jejunum, ileum, or colon in human subjects.

FIGURE 3

An example of a naso-ileal catheter design that can be used for intestinal aspiration and delivery in human subjects. (A) The schematic design includes the cross-sectional view of the different lumina (reproduced with permission from Mui Scientific, Ontario, Canada). Photos show the (B) naso-intestinal catheter with 300-cm tubing, excluding the connector end; (C) multiple lumina, closed with a stopcock and lid; (D) the centimeter indications on the tubing; (E) the deflated balloon and the 3 tip weights; (F) the inflation of the balloon via the balloon channel using a syringe; and (G) the balloon that is inflated with 5 mL of air (maximum capacity 20 mL).

FIGURE 4

Examples of visualization of the catheter tip location using fluoroscopy or X-rays with/without the delivery of contrast liquid in human subjects. Fluoroscopy pictures are (A) without or (B) in combination with the delivery of a contrast liquid, where the contrast liquid appears in black and will follow the direction of the arrows towards the colon. Abdominal X-ray pictures are (C) without or (D) in combination with the delivery of a contrast liquid. Panels C and D were reproduced with permission from Dohil et al. (19). The black line in the pictures is the radio-opaque marker, and 3 small metal (or radio-opaque) weights/markers are located at the tip of the catheter.