Fact-checked by Grok 2 weeks ago

Intraperitoneal injection

Intraperitoneal injection (IP injection) is a and research technique that involves administering a substance, such as a or , directly into the —the serous membrane-lined space within the that contains the , intestines, liver, and other viscera. This route allows for rapid absorption through the peritoneum's extensive vascular and lymphatic network, providing higher local concentrations compared to oral or . In experimental animal studies, particularly with like mice and rats, IP injection is a common method for delivering pharmacological agents, anesthetics, or cells due to its ease of performance, ability to handle larger volumes (up to 10 / body weight), and relatively low on the subject. The procedure typically involves restraining the animal in a , tilting the head downward, and inserting a needle at a shallow angle (about 10–15 degrees) into the lower caudal quadrant of the to avoid organs like the or intestines, ensuring deposition into the rather than solid tissue. Advantages include quick absorption for small molecules via the and suitability for chronic dosing, though can be affected by first-pass hepatic . However, risks encompass inadvertent organ puncture leading to internal , peritoneal , adhesions, or if aseptic techniques are not followed. In human medicine, IP injection is primarily employed for targeted therapies in cancers involving the , such as ovarian, colorectal, gastric, or appendiceal malignancies with , where it delivers high-dose (e.g., , , or ) directly to microscopic or residual tumors post-surgery. Techniques include normothermic postoperative infusions via indwelling catheters or (HIPEC), which circulates heated solutions (41–43°C) intraoperatively for enhanced penetration and . Clinical benefits include prolonged —such as a 16-month increase in median overall for advanced in landmark trials—and effective palliation of malignant —though penetration is limited to tumors less than 1 cm in diameter. Potential complications involve catheter-related infections, bowel , chemical from drug , and systemic side effects due to , necessitating careful patient selection and monitoring.

Definition and Anatomy

Definition

Intraperitoneal injection is the administration of a substance directly into the , the fluid-filled space within the that houses various organs such as the , intestines, and liver, enabling through the peritoneal membranes. This method involves inserting a needle through the to deliver the substance into this cavity, where it can be rapidly taken up by surrounding tissues. Unlike intravenous injection, which delivers substances directly into the bloodstream for immediate systemic distribution, or , which relies on absorption from muscle tissue, intraperitoneal injection utilizes the peritoneum's extensive surface area—approximately 125 cm² in a 200 g —for efficient and systemic uptake. This route avoids gastrointestinal degradation associated with while being simpler and less invasive than intravenous access for repeated dosing in experimental settings. The absorption mechanism primarily involves or through the visceral and parietal mesothelial layers of the , with small molecules (molecular weight <5,000 Da) entering the via mesenteric capillaries and larger molecules absorbed via lymphatic drainage, particularly through diaphragmatic stomata. Pharmacokinetically, this leads to rapid onset, with peak plasma concentrations (C_max) achieved faster than subcutaneous routes but slower than intravenous, and typically ranging from 70% to 100% for small molecules due to partial first-pass hepatic . Common substances administered via this route include fluids for , pharmacological drugs such as anesthetics or chemotherapeutics, nutrients, and diagnostic agents, provided they are non-irritant and to minimize damage.

Peritoneal Cavity

The is the potential space within the , lined by the , a continuous composed of two principal layers: the parietal peritoneum, which adheres to the inner surface of the abdominal and pelvic walls, and the visceral peritoneum, which envelops the abdominal viscera. This membrane structure forms a closed sac that contains a small volume of , secreted by the mesothelial cells, to lubricate organ movement and minimize friction during physiological activities. The cavity encloses several key intraperitoneal organs, including the , liver, , , , and portions of the colon, which are suspended and supported by peritoneal folds. The , a prominent double-layered peritoneal extension, anchors the intestines to the posterior and houses an extensive vascular network of arteries, veins, and lymphatics, facilitating the and distribution of nutrients and fluids from the cavity. In human adults, the peritoneal surface area measures approximately 1-2 , providing a broad interface that supports passive of small solutes, such as electrolytes and low-molecular-weight compounds, across the semipermeable mesothelial barrier driven by concentration gradients. For larger molecules, proteins, and excess fluid, predominantly occurs through lymphatic drainage into the and , preventing accumulation within the cavity. Anatomical variations exist across species, with the in , such as mice and rats, being proportionally larger relative to body size—evidenced by a volume of 0.02–0.1 ml in mice compared to 50-75 ml in s—and offering greater accessibility due to a less obstructive omentum and shallower abdominal depth.

Preparation

Prior to performing an intraperitoneal injection, thorough assessment of the patient or subject is essential to identify contraindications and ensure safety. In both humans and , conditions such as , abdominal adhesions, significant distension, or enlarged organs (e.g., due to tumors or ) contraindicate the procedure, as they increase the risk of complications like organ perforation or . In laboratory , additional evaluation includes checking for recent surgical history or signs of , while in humans—where intraperitoneal injections are typically reserved for specific therapies like —pre-procedure imaging or clinical exams assess patency. is generally not required for uncomplicated intraperitoneal injections in or outpatient human procedures via port, but in humans undergoing associated procedures under or , a 6-8 hour fast may be advised to minimize risk. Essential equipment includes sterile syringes (1-5 mL for small animals, larger for others), needles sized 23-27 gauge for (thinner for mice to minimize trauma, e.g., 25-27G) and 18-23 gauge for larger animals or humans, antiseptic solutions like 70% or for site preparation, disposable gloves, and . For animal subjects, immobilizing devices such as restraint tubes or boards facilitate safe handling, particularly in , to prevent movement during setup. All equipment must be single-use where possible to maintain sterility. The injectate must be prepared to minimize and ensure with the peritoneal . Substances are typically diluted in isotonic solutions like 0.9% saline or to achieve physiological osmolality (approximately 300 mOsm/L), with adjusted to near-neutral (around 7.4) to avoid damage. Volume limits are species-dependent: 10-20 mL/kg body weight in (e.g., maximum 0.25-0.5 mL for a 25 g ), up to 20 mL/kg in larger animals like rats or rabbits, and typically 1-2 L for normothermic IP infusions or 2-6 L for hyperthermic procedures (HIPEC) in humans, adjusted per protocol and patient factors. Pre-warming the solution to body temperature (37°C) reduces discomfort, and for viscous or concentrated drugs, through a 0.22 μm filter ensures sterility if not commercially prepared. Sterility protocols are critical to prevent introducing pathogens into the , which could lead to severe . Aseptic technique involves hand hygiene with soap or alcohol-based sanitizer, donning sterile gloves, and disinfecting the injection vial septa and abdominal site with swabs in a from center outward, allowing to air dry. Work in a clean environment, such as a for hazardous substances, and use a new needle for drawing up the injectate to avoid coring the and contaminating the solution. In animals, clipping fur at the site (if excessive) and avoiding multiple punctures further uphold sterility.

Technique

The technique for intraperitoneal injection involves careful site selection, proper positioning of the subject, precise needle insertion, and controlled administration to ensure delivery into the peritoneal cavity while minimizing risks to organs or vessels. Site selection is critical to avoid vital structures such as the bladder, intestines, liver, or major blood vessels. In laboratory animals like mice and rats, the injection is typically performed in the lower right abdominal quadrant, lateral to the midline and caudal to the umbilicus, to reduce the chance of penetrating the cecum or other organs on the left side. In larger animals or veterinary settings, the lower quadrants of the abdomen are used, avoiding the umbilicus, scars, or any palpable masses, with a quadrant rotation method sometimes employed for repeated injections to promote even distribution. For humans, direct needle injection is uncommon and generally reserved for specific clinical scenarios; instead, access is often via an implanted subcutaneous port or catheter positioned near the rib cage, with the peritoneal entry site surgically determined to target the abdominal cavity broadly. Positioning ensures safe access to the and organ displacement away from the needle path. In humans, the patient is placed in a on a bed or table to facilitate abdominal exposure and relaxation. Local or general may be used depending on the procedure's invasiveness, such as during surgical placement of access devices. In animals, restraint in dorsal recumbency (, abdomen up) is standard, often with the head tilted slightly downward to allow abdominal organs to slide cranially; manual scruffing or / is applied to minimize movement, particularly in or smaller species. The insertion process begins with skin preparation using solutions, followed by needle entry. A 25-30 needle (for ) or larger for bigger animals is inserted at a 15-45 degree angle to surface, directed toward the head or caudally to penetrate the without entering s. is performed by gently pulling back on the to check for blood (indicating vascular puncture) or contents (such as or intestinal ); if present, the needle is withdrawn, and a new one used at an alternative site. In humans, for port-based , a needle is inserted perpendicularly through into the self-sealing port disc, secured with tape, and connected to an infusion line. Once placement is confirmed, the substance is injected slowly over several minutes in animals to allow dispersion and prevent abdominal pressure buildup, followed by needle withdrawal and gentle massage of the site to aid distribution. Volume and administration rate are tailored to the subject's size to avoid leakage, organ compression, or systemic overload. In rodents, volumes are limited to 10-20 mL/kg body weight, administered gradually at rates of 0.5-1 mL per minute to minimize discomfort and ensure absorption. For larger animals, up to 20-25 mL/kg may be used in divided doses if needed and tolerated. In human clinical practice, infusions via catheter can involve 1-2 liters of fluid mixed with medication over 1.5-2 hours to achieve therapeutic concentrations without acute distress. Throughout the process, immediate monitoring for reactions such as respiratory distress, , or signs of organ puncture is essential, with cessation if adverse effects occur.

Post-Administration Care

Following intraperitoneal injection, patients or subjects should be monitored closely for immediate adverse effects to ensure and detect complications early. In both human and animal contexts, observation protocols typically involve assessing such as , , and for 15-30 minutes post-injection, with extended monitoring up to several hours if any distress is noted. Signs of distress to watch for include (manifesting as hunching, writhing, or grimacing in animals; or reported discomfort in humans), or distention, and potential leakage indicated by at the site or . Site management begins immediately after withdrawal of the needle. If bleeding occurs, apply gentle with clean for 20-30 seconds until is achieved, then clean the area with saline or water to prevent . In humans, advise rest in a semi-upright , , and light ambulation to alleviate or from instilled fluid; comfortable clothing with elastic waistbands is recommended. For animals, return the subject to its housing promptly but observe in a quiet, warmed to minimize , with adjustments such as single housing if multi-animal setups could exacerbate . Follow-up care includes thorough documentation of the details, including injected , timing, substance used, and any observed reactions, to inform subsequent administrations. Schedules for repeat doses should be established based on the therapeutic , with imaging or clinical assessments (e.g., for fluid distribution in humans) if the injection is diagnostic. Ongoing monitoring for delayed effects, such as or , is essential, particularly in research settings where animals may require daily health checks. Emergency responses are critical for severe complications like anaphylaxis or organ perforation, often linked to insertion errors such as inadvertent puncture of abdominal structures. For anaphylaxis, administer intramuscular epinephrine (0.3-0.5 mg in adults; 0.01 mg/kg in animals) immediately, followed by supplemental oxygen, fluids, and transfer to an emergency facility for at least 4-6 hours of observation. In cases of suspected perforation leading to peritonitis, initiate broad-spectrum antibiotics (e.g., covering Gram-negative and anaerobic bacteria) intravenously, provide supportive fluids, and prepare for surgical intervention if hemodynamic instability or worsening abdominal signs develop. Veterinary protocols emphasize contacting a specialist immediately for analgesia and further evaluation in animals showing acute pain or shock.

Clinical Applications

In Humans

Intraperitoneal (IP) injection in humans is primarily employed for therapeutic purposes in and . In the treatment of and primary peritoneal malignancies, IP chemotherapy delivers drugs such as directly into the to achieve higher local concentrations at tumor sites, particularly after optimal . This approach has been shown to improve overall survival and compared to intravenous administration alone in patients with stage III ovarian cancer. For instance, regimens involving IP combined with intravenous have demonstrated a median survival benefit of up to 16 months in clinical trials. Additionally, hyperthermic IP chemotherapy (HIPEC), where heated chemotherapeutic agents like or are instilled post-surgery, enhances drug penetration and cytotoxicity for peritoneal metastases. However, subsequent trials, such as the 2018 OVHIPEC study, have shown mixed results, with no significant overall survival benefit in some settings for HIPEC added to . In , a form of IP injection, sterile dialysate solutions are infused into the via an indwelling to facilitate the removal of waste products and excess fluid in patients with end-stage renal disease, mimicking the kidneys' filtration function. Diagnostic applications of IP injection include peritoneography, where contrast media is instilled into the to visualize abnormalities such as hernias, leaks, or adhesions using imaging modalities like or MRI. This technique aids in evaluating complications in patients or detecting occult inguinal hernias in cases of unexplained . Furthermore, IP nutrition, involving the administration of amino acid-based solutions, serves as a supplemental method for nutrient delivery in malnourished patients undergoing or those with gastrointestinal intolerance, providing calories and proteins directly absorbable through the . Efficacy studies indicate that IP administration results in improved local drug concentrations for abdominal malignancies, with peritoneal-to-plasma ratios often exceeding 20:1 for agents like , enhancing antitumor effects while systemic exposure remains controlled. Bioavailability of IP-administered drugs in humans typically ranges from 50% to 90%, depending on the agent and patient factors, allowing for efficient systemic absorption via peritoneal capillaries and lymphatics. Intraperitoneal administration of for advanced is supported by pivotal clinical trials demonstrating its safety and efficacy, leading to recommendations by the . However, contraindications include significant , bowel obstruction, extensive adhesions, or extra-abdominal metastases, as these can increase risks of leakage, , or ineffective distribution.

In Veterinary Medicine

In veterinary medicine, intraperitoneal injection serves as an alternative route for fluid in dehydrated small animals, including dogs and cats, when intravenous access is challenging or unavailable. crystalloid solutions, such as lactated Ringer's, are administered to provide rapid volume expansion and correction of through peritoneal absorption into the systemic circulation. This approach is particularly useful in critically ill patients, allowing delivery of moderate to large fluid volumes (typically 20-30 mL/kg) without requiring vascular catheterization. The technique is also applied for antibiotic administration in small animals with peritoneal infections, such as septic peritonitis in cats and dogs, enabling direct delivery of agents like aminoglycosides or cephalosporins to the affected site for enhanced local efficacy. In such cases, combinations of broad-spectrum antibiotics are instilled post-surgical lavage to reduce bacterial burden and support recovery. Species-specific adaptations are critical for safety and efficacy. In ruminants like calves, the large accommodates higher fluid volumes, up to 40 mL/kg of solutions, making it a viable option for treating moderate in neonates where oral or intravenous routes are impractical. Conversely, intraperitoneal injection is contraindicated in due to the presence of extensive , which pose a high of inadvertent injection leading to respiratory or drowning-like effects. This route offers advantages in through its rapid absorption profile, which is beneficial for stabilization in hypovolemic or septic patients. Ethical considerations in veterinary applications prioritize minimization, guided by Institutional Animal Care and Use Committee (IACUC) protocols adapted for clinical settings, which recommend or local anesthetics prior to injection and vigilant monitoring for signs of distress to ensure humane procedure execution.

Research Applications

In Laboratory Animals

Intraperitoneal () injection is a primary method for administering substances in experimental animal , particularly in such as mice and rats, where it facilitates rapid systemic for drug testing, toxicity assessments, efficacy trials, and model induction. In toxicity studies, IP administration allows evaluation of dose-dependent effects, such as determining the LD50 of compounds like in mice, where particle size influences lethality (189 mg/kg for small particles versus 288 mg/kg for larger ones). For trials, the route supports delivery of macromolecules like IgG-TNF or recombinant , often achieving higher compared to subcutaneous injection. models benefit from the peritoneal cavity's large surface area, enabling efficient dissemination, as seen in simulations using bacterial inocula. Standardization of injection protocols is essential to ensure and minimize variability in laboratory . In mice, the maximum recommended volume is typically 10 mL/kg body weight, equating to about 0.25 mL for a 25 g animal, while similar limits apply to (e.g., 2.5 mL for a 250 g rat). The involves restraining the animal in a head-down position, inserting a 25-27 needle into the lower right abdominal at a 10-30° angle toward the head to avoid organs like the or liver, and injecting slowly to prevent leakage. (2-4% induction, 0.5-1.5% maintenance) is commonly employed to reduce stress and facilitate handling during the procedure, particularly for repeated administrations. Ethical frameworks guide the use of IP injection in animal research, emphasizing the 3Rs principle—replacement, reduction, and refinement—to promote humane practices. seeks non-animal alternatives where feasible; minimizes animal numbers through optimized study design; and refinement improves procedures to lessen pain, such as using and precise techniques to avoid peritoneal irritation. Publications involving IP injections must adhere to reporting standards like the ARRIVE guidelines, which require detailing randomization, blinding, and welfare considerations to enhance transparency and reproducibility. Representative examples illustrate IP injection's utility in specific models. In peritonitis research, IP administration of zymosan A (0.1-1 mg per ) induces acute in mice, mimicking aspects of bacterial . Alternatively, hog gastric induces acute in mice, mimicking bacterial with monitored survival rates up to 24 hours post-injection. For studies, IP insulin tolerance tests assess glucose ; mice are acclimated to handling before receiving 0.55-0.75 IU/kg insulin, with glucose monitored at intervals to evaluate insulin without excessive stress.

In Pharmacological Studies

Intraperitoneal (IP) injection offers distinct pharmacokinetic advantages in pharmacological studies, primarily by bypassing gastrointestinal first-pass while still subjecting drugs absorbed via the portal system to hepatic . This route enables rapid systemic absorption through the extensive peritoneal surface area, with small molecules often detectable in circulation within seconds and absorption half-lives typically ranging from 10 to 30 minutes for many drugs, facilitating quicker onset compared to . In bioavailability studies, IP injection frequently demonstrates superior pharmacokinetics relative to oral routes, achieving higher absolute bioavailability (F%)—for instance, 69% for in mice versus approximately 2.8% orally—due to avoidance of gut and variable . Compared to intravenous () administration, IP yields comparable bioavailability but with slightly delayed peak concentrations, as seen with (F% ≈ 105% IP versus IV). These comparisons are central to evaluating formulations, particularly for poorly bioavailable compounds like deramciclane, where IP F% reached 18.49% against 3.42% orally in rats. IP injection has proven valuable in nanoparticle delivery systems for targeted therapies, enhancing tumor accumulation and penetration in peritoneal malignancies. For example, uPAR-targeted nanoparticles administered IP accumulated 17% of the injected dose per gram in orthotopic pancreatic tumors—threefold higher than IV delivery—while carrying chemotherapeutics like or to inhibit tumor growth by 40-71.5% without systemic toxicity. Key findings highlight enhanced efficacy of biologics via , such as monoclonal antibodies, which achieve significant therapeutic effects in preclinical models; intraperitoneal injection of anti-amyloid-β antibody mE8-IgG2a reduced Aβ plaques in a dose-dependent manner in PDAPP mice without inducing microhemorrhages. Similarly, IP administration of neutralizing anti-H5N1 monoclonal antibodies provided prophylactic and therapeutic protection in murine infection models. However, limitations in protein stability persist, as biologics may degrade in the peritoneal milieu due to enzymatic exposure or variations, necessitating strategies to maintain integrity during . Translational research leverages IP data from animal studies to inform human trials through dose extrapolation, commonly using body surface area (BSA) scaling via allometric principles. The human equivalent dose (HED) is calculated as HED (mg/kg) = animal dose (mg/kg) × (animal K_m / human K_m), where K_m factors (e.g., 6 for rats, 37 for humans) normalize for metabolic differences, enabling safe starting doses after applying safety factors like division by 10. This approach, recommended by regulatory guidelines, supports progression from rodent IP pharmacokinetics to clinical dosing while accounting for route-specific absorption.

Advantages and Risks

Benefits

Intraperitoneal injection leverages the large surface area of the , approximately 125 cm² in rats, to facilitate rapid absorption of administered substances into the systemic circulation without requiring direct vascular access. This route is particularly advantageous in volume-limited scenarios, allowing for the safe delivery of larger fluid volumes—up to 10–20 mL/kg body weight in (e.g., 0.2–0.5 mL in mice)—compared to routes constrained by tissue capacity. The abundant blood supply and microvilli in the enable efficient diffusion into capillaries and lymphatics, achieving high for various compounds, such as 69% for in preclinical studies. For targeted delivery, intraperitoneal injection provides elevated local concentrations in the , which is beneficial for treating peritoneal diseases and reduces systemic toxicity, especially in applications. This approach exposes tumors to higher drug levels while minimizing exposure to distant healthy tissues, as the peritoneal-plasma barrier limits drug from the cavity to the bloodstream. In pharmacological studies, this has demonstrated improved therapeutic efficacy with lower overall toxicity profiles for agents like in models. The technique's accessibility stems from its relative simplicity compared to surgical routes, requiring minimal specialized equipment and being easier to master for repeated administrations in research and veterinary settings. It is particularly cost-effective for small animals like rodents, utilizing inexpensive, widely available solutions without the need for anesthesia or advanced facilities. In veterinary medicine, organizations such as the World Small Animal Veterinary Association endorse intraperitoneal analgesia as a straightforward and economical method for postoperative pain management in procedures like ovariohysterectomy. Comparative pharmacokinetic data highlight intraperitoneal injection's advantages over , with faster absorption rates leading to quicker onset of effects. For instance, small molecules appear in systemic circulation within 10 seconds post-intraperitoneal injection versus 60 seconds subcutaneously. In insulin delivery studies among patients with non-insulin-dependent diabetes mellitus, intraperitoneal administration achieved higher peak insulin levels and increased glucose utilization rates by approximately 50% (to 3.91 mg/kg/min from 2.60 mg/kg/min), compared to slower and less pronounced responses subcutaneously. Overall, intraperitoneal routes often yield higher maximum concentrations (Cmax) and shorter times to peak (tmax) for small molecules, with (AUC) values substantially elevated for macromolecules relative to subcutaneous delivery.

Complications and Limitations

Intraperitoneal injection carries several acute risks, primarily related to procedural errors and the introduction of substances into the . Organ perforation, such as laceration of the intestines, , or major vessels, can occur if the needle penetrates vital structures, leading to immediate bleeding, , or secondary complications like within 12-48 hours. In laboratory rodents, misinjection rates—where the needle enters unintended sites like the or subcutaneous tissues—range from 3% to 100%, with pilot studies reporting up to 24% overall, increasing the likelihood of such perforations. , often chemical or bacterial in origin, arises from during injection, gastrointestinal leakage, or by non-sterile or acidic substances, manifesting as , , and of the peritoneal wall and mesenteric fat. Chemical from injected agents can further promote adhesions between visceral organs, exacerbating and potentially causing or abscesses, as observed in histopathological examinations of mice following repeated injections. Systemic complications stem from the route's pharmacokinetic profile, which introduces variability and delays compared to other methods. Absorption from the is generally rapid due to the large surface area but highly variable, influenced by factors like substance , volume, and first-pass hepatic , potentially leading to inconsistent levels and overdose risks if dosing is not precisely calibrated. This variability can result in uneven , where misinjected doses absorb more slowly or erratically, heightening in sensitive models. Additionally, intraperitoneal injection provides slower onset than intravenous administration, making it unsuitable for emergencies requiring immediate systemic effects, as peritoneal typically takes minutes longer to achieve peak concentrations. Certain conditions contraindicate intraperitoneal injection to avoid amplified risks. In humans, particularly during intraperitoneal for , it is contraindicated in cases of active abdominal , extensive adhesions from recent , or uncorrectable coagulopathies, which elevate bleeding and hazards. poses a significant contraindication due to potential fetal exposure and heightened risks from anatomical changes. Immunocompromised patients face higher rates post-injection, with catheter-related complications like occurring more frequently in such populations. In veterinary and research settings, similar contraindications apply, including recent abdominal or coagulopathies in animals, where incidence may reach 1-5% in untrained hands. Mitigation strategies can reduce these risks, though the procedure demands expertise. In human applications, such as , ultrasound guidance facilitates direct puncture and minimizes perforation by visualizing the peritoneal space, improving safety and feasibility. For animals, operator training, post-injection monitoring for signs like or pain, and validation of injection sites via necropsy are essential to detect and address complications early. Despite these measures, remains a notable limitation, with studies in showing scores significantly elevated after repeated injections compared to controls.

History

Early Development

The concept of intraperitoneal injection emerged in the as an experimental therapeutic approach, with one of the earliest recorded instances occurring in 1744 when English physician Christopher Warrick administered a mixture of Bristol water and directly into the of a suffering from dropsy (), aiming to deliver locally to the abdominal region. Although rudimentary and lacking modern sterility, this marked an initial exploration of the peritoneal route for , predating more systematic medical applications. By the late , advances in , pioneered by figures such as Scottish Lawson Tait, facilitated greater understanding of peritoneal access during procedures like ovariotomy and of pelvic conditions in the , though these primarily involved drainage for rather than active injection. Tait's work on aseptic techniques in abdominal operations laid foundational knowledge for later invasive peritoneal interventions, emphasizing the need for cleanliness to mitigate risks in the peritoneal space. In the early 20th century, intraperitoneal injection gained traction in animal experimentation, particularly for nutrient and fluid administration. By the 1900s, researchers employed the route in laboratory animals to deliver saline solutions and nutrients, leveraging the peritoneum's for rapid systemic effects in studies of and . A notable veterinary milestone occurred in 1892 in , where intraperitoneal injection was first utilized for anesthetic agents like in animals, providing an alternative to oral or rectal routes and influencing early protocols for and experimental subjects. In human applications, pediatricians Kenneth D. Blackfan and Kenneth F. Maxcy introduced intraperitoneal saline infusions in 1918 to treat and in infants, demonstrating the method's utility for volume replacement when intravenous access was challenging. These experiments highlighted the route's potential for quick absorption but also underscored anatomical considerations, such as avoiding vascular or organ puncture based on contemporaneous peritoneal knowledge. Key contributions to intraperitoneal injection's development came from surgeons addressing and metabolic disorders in the 1910s. American surgeon , renowned for his work on surgical during the early , incorporated fluid resuscitation techniques to counteract , though his primary innovations focused on direct blood transfusions and adrenaline use. Initial veterinary applications extended to in the early , where intraperitoneal routes were explored for nutrient supplementation and basic therapeutics in large animals like , aiding in field-based treatments amid limited intravenous options. Prior to 1950, intraperitoneal injection faced significant challenges, primarily high infection rates stemming from inadequate sterility practices in the pre-antibiotic era. Peritoneal contamination often led to , with historical mortality rates approaching 100% for secondary infections in the early , limiting the procedure's adoption to desperate cases like severe . Poor aseptic techniques, reliance on non-sterile fluids, and limited understanding of bacterial exacerbated these risks, confining widespread use to controlled experimental settings until improvements in sterilization and antimicrobial agents emerged.

Modern Uses

Following , intraperitoneal injection saw significant integration into clinical practices, particularly in the management of renal failure through . In 1960, introduced the first commercially available peritoneal dialysis solution, enabling more reliable and standardized infusion of dialysate into the to filter waste from the via the peritoneal membrane. This advancement built on earlier experimental work from the and , where intermittent became established as a viable using polyethylene and catheters. Concurrently, the marked the emergence of intraperitoneal chemotherapy protocols, with the U.S. pioneering the concept of locoregional intraperitoneal to target peritoneal malignancies more effectively than . These protocols laid the groundwork for (HIPEC), first clinically applied in 1980 by for , involving heated chemotherapeutic agents delivered directly into the post-cytoreductive surgery to enhance tumor penetration and efficacy against . Technological improvements in the late 20th and early 21st centuries further refined intraperitoneal injection for precision and patient safety. Implantable ports, initially developed for venous access in oncology around 1983, were adapted for peritoneal use by the 1990s to facilitate repeated infusions with reduced infection risk and procedural discomfort; these subcutaneous devices connect to peritoneal catheters, allowing needle access through a self-sealing septum. By the 2000s, nanoparticle-based enhancements transformed drug delivery, enabling targeted and controlled release within the peritoneal space; for instance, superparamagnetic iron oxide nanoparticles labeled with high-density lipoprotein improved uptake and imaging of peritoneal tumors when administered intraperitoneally. Robotic assistance emerged in the 2010s and 2020s to enhance procedural accuracy, with CT-guided robotic systems achieving sub-millimeter precision for needle placements in peritoneal interventions, minimizing trauma and improving outcomes in minimally invasive settings. Additionally, fully implantable robotic devices for intraperitoneal microinfusion, refilled minimally invasively, were prototyped by 2021 to support programmable, long-term drug delivery. Regulatory milestones in the 1980s emphasized safe injection practices, influencing intraperitoneal applications through broader (WHO) guidelines on injection safety and , which promoted sterile techniques and standardized equipment to prevent complications like in and contexts. From the 2010s onward, research expanded into via intraperitoneal routes, leveraging vectors like serotype rh.10 for muscle and chimeric antigen receptor () T-cell delivery to eradicate established peritoneal ovarian tumors in preclinical models. These approaches demonstrated durable expression and antitumor , with intraperitoneal administration achieving higher local concentrations than systemic methods. As of 2025, recent trends incorporate (AI) for optimized dosing and biodegradable injectates for sustained release, enhancing therapeutic precision in peritoneal applications. AI-driven models now guide personalized dosing in precision oncology, integrating real-time imaging and to predict optimal intraperitoneal infusion rates for , reducing toxicity while maximizing tumor exposure. Complementing this, biodegradable nanoparticles and hydrogels enable prolonged drug release; for example, gelatin-silica hybrids provide sustained elution over weeks, while exosome-engineered hydrogels mitigate peritoneal adhesions through effects post-injection. Similarly, MDM2-siRNA-loaded biodegradable nanoparticles, administered intraperitoneally, have extended survival in peritoneal dissemination models by inhibiting tumor growth over extended periods. These innovations underscore a shift toward minimally invasive, intelligent systems for chronic peritoneal therapies.

References

  1. [1]
    Intraperitoneal Route of Drug Administration: Should it Be Used in ...
    Dec 23, 2019 · One of the more commonly used routes in rodent studies is the IP route where a pharmacological agent is injected into peritoneal cavity. This ...Missing: definition | Show results with:definition
  2. [2]
    Intraperitoneal therapy for peritoneal cancer - PMC - NIH
    The use of an IP catheter is associated with a higher risk of infection and fever, and occasionally physical damages to peritoneal tissues (e.g., perforation).Intraperitoneal Therapy For... · Clinical Research On Ip... · Pk Model Of Disposition Of...<|control11|><|separator|>
  3. [3]
    Intraperitoneal Injection - an overview | ScienceDirect Topics
    In the context of Neuroscience, 'Intraperitoneal Injection' refers to the technique of administering drugs into the peritoneal cavity of rodents.
  4. [4]
    Peritoneum: Anatomy, Function, Location & Definition
    Apr 27, 2022 · Your peritoneum is a membrane that lines the inside of your abdomen and pelvis (parietal layer). It also covers many of your organs inside (visceral layer).
  5. [5]
  6. [6]
    Anatomy, Abdomen and Pelvis, Peritoneum - StatPearls - NCBI - NIH
    The peritoneal cavity contains the omentum, ligaments, and mesentery. Intraperitoneal organs include the stomach, spleen, liver, first and fourth parts of the ...
  7. [7]
  8. [8]
    Functional vascular anatomy of the peritoneum in health and disease
    The visceral peritoneum drains into the portal vein. Drugs absorbed are subject to first-pass hepatic metabolism. Peritoneal inflammation and cancer invasion ...
  9. [9]
    Physiology of Peritoneal Dialysis | Abdominal Key
    Jun 16, 2016 · It has a surface area that is similar to body surface area, and so typically ranges from 1 to 2 m2 in an adult. The peritoneum is divided ...
  10. [10]
    Mechanisms of solute clearance and ultrafiltration in peritoneal ...
    Sep 6, 2024 · To emphasize that the movement of solutes across the peritoneal membrane occurs by passive diffusion rather than an active process, some ...
  11. [11]
    Animal models in peritoneal dialysis - PMC - NIH
    On the other hand, the parietal peritoneum that is directly related to the solute transport is larger in rats than in humans, while in rabbits it is similar to ...Missing: rodents relative
  12. [12]
    Administration of Substances to Laboratory Animals - PubMed Central
    The technique requires animals to be sedated heavily and given a local anesthetic block over the spinal needle insertion site; alternatively animals can undergo ...
  13. [13]
    Intraperitoneal Injection - an overview | ScienceDirect Topics
    Intraperitoneal injection carries the risk of causing internal injury or of misplaced injection into a blood vessel or an organ, particularly the large thin- ...
  14. [14]
    [PDF] mouse-handling-and-techniques.pdf - UNC Research
    Basics and a few tips. • Use a fresh, sterile needle for each injection; do not reuse needles between animals ... Figure 10: Target IP Injection Site.
  15. [15]
    [PDF] Injection Routes, Maximum Needle Sizes & Volumes - NIH OACU
    Rear Leg/Thigh. Volume: <0.05ml. Needle: <23 Gauge. Abdomen - Lower Quadrant. Volume: <2-3ml. Needle: <21 Gauge. Lateral Tail Vein. Volume: <0.2ml.
  16. [16]
    [PDF] Intraperitoneal (IP) Injection in Rats and Mice SOP
    This Standard Operating Procedure (SOP) describes the procedure of intraperitoneal (IP) injection in rats and mice. This SOP follows the CCAC guidelines for ...
  17. [17]
    [PDF] A good practice guide to the administration of substances and ...
    7 The smallest needle size should be used, taking into account the dose volume, viscosity of injection material, speed of injection and species. Subcutaneous.Missing: preparation steps
  18. [18]
    Guidelines on Administration of Substances to Laboratory Animals
    If pH is outside of physiologic range, administer the substance through a central vessel (such as the jugular or femoral vein) or buffer the solution such that ...
  19. [19]
    [PDF] Intraperitoneal injections of IVISbrite D-Luciferin - Revvity
    Prep the site with 70% ethanol. Injection. Needle should be bevel-side up and slightly angled. 15 - 20 degrees when entering the abdominal cavity ...Missing: humans | Show results with:humans
  20. [20]
    Standard for Administered Agents - UNC Policies
    V. Preparations, solubility, and safety of solutions. All solutions administered via injection to laboratory animals should be sterile and free of pathogens.
  21. [21]
    [PDF] SOP: Mouse Intraperitoneal Injection
    Dec 12, 2017 · Intraperitoneal (IP) injections should be made into the animal's right abdominal quadrant so as to avoid penetrating the cecum on the left side.
  22. [22]
    [PDF] Intraperitoneal IP Injections - UGA research
    The aim of this technique is to administer material into the space surrounding the abdominal organs, avoiding injection directly into any organ. Restrain ...<|control11|><|separator|>
  23. [23]
    [PDF] Injection Techniques, Restraint, & Handling for Mice and Rats
    When performing the IP injection on the rat you should inject into the lower right quadrant of the abdomen to avoid hitting such organs as liver, bladder, and ...
  24. [24]
    About Intraperitoneal (IP) Chemotherapy
    During IP chemotherapy, the medicine will just target the cancer in your peritoneal space. This treatment uses a higher dose of chemotherapy medication to do ...Missing: definition | Show results with:definition
  25. [25]
    Preventing and Managing Adverse Reactions - CDC
    Jul 25, 2024 · Because anaphylaxis may recur after patients begin to recover, monitoring in a medical facility for several hours is advised, even after ...
  26. [26]
    None
    ### Summary of Post-Injection Care, Monitoring, Signs of Distress, Emergency Responses, and Follow-Up for IP Injections in Mice
  27. [27]
    None
    ### Summary of Observation Protocols, Site Management, Follow-Up, and Emergency Responses After IP Injection in Rats and Mice
  28. [28]
    Treatment of Ovarian Epithelial, Fallopian, & Peritoneal Cancers - NCI
    Nov 22, 2024 · In IP chemotherapy, the anticancer drugs are carried directly into the peritoneal cavity (the space that contains the abdominal organs) through ...
  29. [29]
    Clinical Practice Guidelines : Anaphylaxis
    Oct 17, 2025 · All children with anaphylaxis should be observed in a setting equipped to manage deterioration, for at least 4 hours: After last dose of ...<|control11|><|separator|>
  30. [30]
    Gastric Perforation - StatPearls - NCBI Bookshelf
    Initial management consists of aggressive resuscitation, oxygen therapy, intravenous fluids, and broad-spectrum antibiotics.
  31. [31]
    Intestinal Perforation Treatment & Management - Medscape Reference
    Sep 3, 2024 · Antibiotics have proved effective in decreasing the rate of postoperative wound infection and improving outcomes in patients with intraperitoneal infection and ...
  32. [32]
    Fluid Therapy for Critically Ill Dogs and Cats - WSAVA2005 - VIN
    Intravenous infusion is the preferred means of delivering fluids to severely dehydrated animals and medium to large dogs. It allows for a controlled delivery ...
  33. [33]
    Therapeutic interventions using the peritoneal and coelomic cavity ...
    Apr 30, 2024 · ANIMALS. Dogs, cats, and exotic pets. METHODS. Peritoneal and coelomic centesis allows for delivery of fluids or to perform euthanasia.
  34. [34]
    A survey of antimicrobial use during bovine abdominal surgery by ...
    Intraperitoneal antimicrobials are also used in animal species, including dogs, rabbits, and fish (8–11).Introduction · Results · Discussion
  35. [35]
    Management of Peritonitis - VIN
    A combination of a penicillin or cephalosporin with an aminoglycocide antibiotic is recommended in animals without pre-existing renal disease. Cefazolin (Ancef, ...
  36. [36]
    Intraperitoneal fluid administration to neonatal calves - PubMed
    Jul 24, 2025 · Intraperitoneal fluid therapy is a viable treatment option for moderately dehydrated calves. Clinical relevance: Fluid therapy is indicated ...
  37. [37]
    Intraperitoneal fluid administration to neonatal calves in
    Jul 24, 2025 · Fluid therapy is indicated in dehydrated calves primarily for volume replacement and when more than 8 days old for correcting acid-base ...
  38. [38]
  39. [39]
    Critical care for sick cattle-practical IV therapy (Proceedings) | dvm360
    Isotonic solutions can be administered by the intravenous, intraperitoneal, subcutaneous, and intraosseous routes, whereas hypertonic solutions should only be ...
  40. [40]
    Use of serial measurements of peritoneal fluid lactate concentration ...
    May 15, 2012 · Study population—The following cases were included in the study: horses referred to the Equine Medical Center of Ocala with colic that had ≥ 2 ...Missing: intraperitoneal injection
  41. [41]
    Analgesia (Guideline) - Vertebrate Animal Research
    Jul 17, 2023 · The purpose of these guidelines is to describe appropriate analgesia regimens for the management of pain in animals used in teaching, research and testing.
  42. [42]
    [PDF] Guideline for Pain and/or Distress in Laboratory Animals - NIH OACU
    The IC ACUC must ensure that all aspects of the Animal Study Proposal (ASP) that may cause more than transient pain and/or distress are addressed; alternatives2 ...Missing: injection | Show results with:injection
  43. [43]
    Intraperitoneal Continuous-Rate Infusion for the Maintenance ... - NIH
    Intraperitoneal injectable anesthetics are often used to achieve surgical anesthesia in laboratory mice. Because bolus redosing of injectable anesthetics ...
  44. [44]
    The 3Rs - NC3Rs
    The principles of the 3Rs (Replacement, Reduction and Refinement) were developed over 50 years ago providing a framework for performing more humane animal ...
  45. [45]
    ARRIVE Guidelines: Home
    The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) are a checklist of recommendations for the full and transparent reporting of research ...Guidelines 2.0 · The ARRIVE study plan · Author checklists · About
  46. [46]
    Establishment of Experimental Murine Peritonitis Model with Hog ...
    Mar 6, 2017 · The survival rates of mice were monitored for up to 24 h at 0, 12, and 24 h after the intraperitoneal bacterial injection. Mice that ...
  47. [47]
    Acclimation Prior to an Intraperitoneal Insulin Tolerance Test to ...
    We describe a method to acclimate the mice to handling, injections and blood sampling prior to performing the insulin tolerance test in order to limit stress- ...
  48. [48]
    Intraperitoneal - an overview | ScienceDirect Topics
    Animal. Intraperitoneal injections of chloramphenicol at 20, 40, or 100 mg kg−1 for 3 months in mice have been reported to cause splenomegaly, hepatomegaly, ...Missing: emergency | Show results with:emergency
  49. [49]
    Oral, intraperitoneal and intravenous pharmacokinetics of ... - PubMed
    The absolute bioavailability of deramciclane in rats was 3.42% after oral and 18.49% after intraperitoneal administration. The comparative pharmacokinetic study ...
  50. [50]
    Tumor Penetrating Theranostic Nanoparticles for Enhancement of ...
    Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, ...
  51. [51]
    Anti-Amyloid Monoclonal Antibodies for the Treatment of Alzheimer's ...
    Nov 13, 2023 · Following intraperitoneal injection of mE8-IgG2a, significant reduction in Aβ plaque was reported in a dose-dependent manner; treatment was ...
  52. [52]
    Prophylactic and Therapeutic Efficacy of Human Monoclonal ...
    We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection.
  53. [53]
    A simple practice guide for dose conversion between animals ... - NIH
    This review provides basic information about translation of doses between species and estimation of starting dose for clinical trials using allometric scaling.
  54. [54]
  55. [55]
  56. [56]
  57. [57]
    Intraperitoneal and incisional analgesia in small animals: simple ...
    Nov 18, 2019 · This second article discusses the use of intraperitoneal and incisional analgesia in small animal practice, including their limitations and recommendations by ...Missing: injection | Show results with:injection
  58. [58]
    Acute effects of intraperitoneal versus subcutaneous insulin delivery ...
    In patients with NIDDM, intraperitoneal insulin injection achieves more rapid and greater peak values for stimulation of glucose Rd than subcutaneous ...
  59. [59]
    None
    ### Summary of Position Statement on Intraperitoneal Injections in Rodents
  60. [60]
    Effects of Repeated Intraperitoneal Injection of Pharmaceutical ... - NIH
    Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in ...
  61. [61]
    Injections and Dosing - Preclinical Research Unit
    Unskilled dosing and injection can cause a wide variety of adverse effects including inefficacy of your model and/or chronic health issues in your animals.
  62. [62]
    Guidelines for Laparoscopic Peritoneal Dialysis Access Surgery
    PATIENT SELECTION. Guideline recommendation. Contraindications for laparoscopic PD catheter placement include active abdominal infection and uncorrectable ...<|separator|>
  63. [63]
    Intraperitoneal Hemorrhage in a Pregnant Woman with ... - NIH
    Jul 26, 2016 · Hyperemesis gravidarum can cause various vitamin deficiencies. Vitamin K deficiency can lead to coagulopathy or hemorrhagic diathesis.Missing: contraindications humans
  64. [64]
    Complications and risk factors for complications of implanted ...
    There were 57 patients who experienced port complications, including infection, subcutaneous liquid accumulation, port rotation, wound dehiscence, inflow ...
  65. [65]
    Intraperitoneal chemotherapy by ultrasound-guided direct puncture ...
    The administration of IP chemotherapy with a direct puncture, under ultrasound guidance, for patients with ROC, is a safe and feasible method, ...
  66. [66]
    Intraperitoneal drug delivery systems for peritoneal carcinomatosis
    The present review aims to offer an overview of the advances and current designs of DDS for PC chemotherapy administration.
  67. [67]
    Robert Lawson Tait (1845–1899) | Embryo Project Encyclopedia
    Aug 27, 2024 · In the early 1880s, Tait began treating ruptured ectopic pregnancies, and by 1883, Tait was one of the first to successfully treat the ...Missing: intraperitoneal injection ascites
  68. [68]
    Robert Lawson Tait (1845–1899): The true innovator of aseptic ...
    Dec 19, 2022 · In 1886, he was able to report one of the most remarkable series in the history of surgery, 139 consecutive ovariotomies without a single death.Missing: intraperitoneal | Show results with:intraperitoneal
  69. [69]
    Early history of parenteral nutrition - PubMed - NIH
    A historical review is presented of a number of aspects of early animal experiments and clinical trials dealing with the iv infusion of whole blood and milk.Missing: intraperitoneal 1900s
  70. [70]
    THE HAZARDS OF INTRAPERITONEAL INJECTIONS - JAMA Network
    Blackfan, K. D., and Maxcy, K. F.: The Intraperitoneal Injection of Saline Solution , Am. J. Dis. Child. 15:19 ( (Jan.) ) 1918. 2. McLean, Stanford, and ...Missing: technique | Show results with:technique<|control11|><|separator|>
  71. [71]
    Resuscitation great. George W. Crile: a visionary mind in ... - PubMed
    Crile dedicated his research years to the study of shock, cardiac arrest, and the use of adrenaline. His research on shock and cardiac arrest led to treatment ...Missing: intraperitoneal injection 1910s
  72. [72]
    A History of Veterinary Anesthesia
    Mar 21, 2017 · Veterinary anesthesiology did not exist as a discipline before 1950. Surgeons and general practitioners gave anesthesia as part of their ...
  73. [73]
    The Discovery of Insulin: An Important Milestone in the History of ...
    Oct 23, 2018 · The discovery of insulin has been a milestone and has truly revolutionized both the therapy and the prognosis of the diabetes.Missing: intraperitoneal | Show results with:intraperitoneal
  74. [74]
    Infections within the Peritoneal Cavity: A Historical Perspective
    Despite the fact that peritonitis was extremely common, reports of successful surgical interventions were only anecdotal before the past century. Medicine's ...Missing: intraperitoneal injection
  75. [75]
    Infections within the peritoneal cavity: a historical perspective
    Despite this, the mortality rates for patients with secondary peritonitis have fallen in the last century from almost 100 per cent to less than 10 per cent.Missing: injection early
  76. [76]
    Our History | Baxter
    1960: We introduced the first peritoneal dialysis (PD) solution. PD filters waste from the blood of people in renal failure through their peritoneal membrane ...Our History · Innovative Beginnings · Industry BreakthroughsMissing: intraperitoneal | Show results with:intraperitoneal
  77. [77]
    History of peritoneal access development - PubMed
    In the 1950s, intermittent peritoneal dialysis was established as the preferred technique; polyethylene and nylon catheters became commercially available and ...
  78. [78]
    A critical analysis of the cytoreductive surgery with hyperthermic ...
    Oct 20, 2016 · The concept of IP chemotherapy was brought forth in the American National Cancer Institute in 1970. In 1978, Dedrick (8) established the ...Hipec In The Clinical... · Crs + Hipec Clinical... · Crs + Hipec: Broader...
  79. [79]
    Past, Present, and Future of Hyperthermic Intraperitoneal ... - NIH
    Jun 10, 2021 · HIPEC was first introduced by John Spratt in 1980 [14]. He treated a pseudomyxoma peritonei patient with intraperitoneal thiotepa followed by ...
  80. [80]
    US20070073250A1 - Implantable port - Google Patents
    First introduced in 1983, implantable access ports have become a standard of use in the treatment of patients with oncological diseases. In addition to oncology ...Missing: intraperitoneal | Show results with:intraperitoneal
  81. [81]
    Intraperitoneal Injection Improves the Uptake of Nanoparticle ...
    Especially molecular imaging has the potential to identify vulnerable and high-risk plaques by diagnosing early atherosclerotic lesions and by accurately ...
  82. [82]
    Feasibility, safety and accuracy of a CT-guided robotic assistance for ...
    Mar 4, 2021 · The aim of this study was to evaluate the feasibility, safety and accuracy of a CT-guided robotic assistance for in-vivo percutaneous needle ...
  83. [83]
    A fully implantable device for intraperitoneal drug delivery refilled by ...
    Aug 11, 2021 · Once refilled, the device acts as a programmable microinfusion system for precise intraperitoneal delivery. The robotic device is grounded ...
  84. [84]
    Successful Eradication of Established Peritoneal Ovarian Tumors in ...
    We have generated several CARs targeted to the retained extracellular domain of MUC16, termed MUC-CD, an antigen expressed on most ovarian carcinomas.
  85. [85]
    Emerging artificial intelligence-driven precision therapies in tumor ...
    Apr 23, 2025 · AI models are expected to pioneer new therapy strategies to mitigate tumor drug resistance, improve efficacy and patient survival, and provide novel ...
  86. [86]
    Sustained Antibiotic Release from Biodegradable Gelatin–Silica ...
    Aug 28, 2024 · A gelatin–silica hybrid is developed as a carrier to facilitate controlled degradation and ensure the sustained, homogeneous release of ...Missing: injectates | Show results with:injectates
  87. [87]
    Biodegradable Nanoparticles Encapsulating Murine Double Minute ...
    Sep 12, 2025 · Intraperitoneal injection of the MDM2-siRNA complex significantly prolonged the survival time of the peritoneal dissemination model mice (p < ...<|control11|><|separator|>