Intraperitoneal injection

Last updated
Intraperitoneal injection
Peritoneal Cavity Human1.jpg
Other namesIP injection
ICD-9-CM 54.96-54.97

Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). It is more often applied to non-human animals than to humans. In general, it is preferred when large amounts of blood replacement fluids are needed or when low blood pressure or other problems prevent the use of a suitable blood vessel for intravenous injection.[ citation needed ]

Contents

In humans, the method is widely used to administer chemotherapy drugs to treat some cancers, particularly ovarian cancer. Although controversial, intraperitoneal use in ovarian cancer has been recommended as a standard of care. [1] Fluids are injected intraperitoneally in infants, also used for peritoneal dialysis.[ citation needed ]

Background

Intraperitoneal injections are a way to administer therapeutics and drugs through a peritoneal route (body cavity). They are one of the few ways drugs can be administered through injection, and have uses in research involving animals, drug administration to treat ovarian cancers, and much more. Understanding when intraperitoneal injections can be utilized and in what applications is beneficial to advance current drug delivery methods and provide avenues for further research. The benefit of administering drugs intraperitoneally is the ability for the peritoneal cavity to absorb large amounts of a drug quickly. A disadvantage of using intraperitoneal injections is that they can have a large variability in effectiveness and misinjection. [2] Intraperitoneal injections can be similar to oral administration in that hepatic metabolism could occur in both.

Early Uses

There are few accounts of the use of intraperitoneal injections prior to 1970. One of the earliest recorded uses of IP injections involved the insemination of a guinea-pig in 1957. [3] The study however did not find an increase in conception rate when compared to mating. In that same year, a study injected egg whites intraperitoneally into rats to study changes in "droplet" fractions in kidney cells. The study showed that the number of small droplets decreased after administration of the egg whites, indicating that they have been changed to large droplets. [4] In 1964, a study delivered chemical agents such as acetic acid, bradykinin, and kaolin to mice intraperitoneally in order to study a "squirming" response. [5] In 1967, the production of amnesia was studied through an injection of physostigmine. [6] In 1968, melatonin was delivered to rats intraperitoneally in order to study how brain serotonin would be affected in the midbrain. [7] In 1969, errors depending on a variety of techniques of administering IP injections were analyzed, and a 12% error in placement was found when using a one-man procedure versus a 1.2% error when using a two-man procedure. [8]

A good example of how intraperitoneal injections work is depicted through "The distribution of salicylate in mouse tissues after intraperitoneal injection" because it includes information on how a drug can travel to the blood, liver, brain, kidney, heart, spleen, diaphragm, and skeletal muscle once it has been injected intraperitoneally. [9]

These early uses of Intraperitoneal injections provide good examples of how the delivery method can be used, and provides a base for future studies on how to properly inject mice for research.

Use in Humans

There are few examples of the use of intraperitoneal injections in humans cited in literature because it is mainly used to study the effects of drugs in mice. The few examples that do exist pertain to the treatment of pancreatic/ovarian cancers and injections of other drugs in clinical trials. One study utilized IP injections to study pain in the abdomen after a hysterectomy when administering anesthetic continuously vs patient-controlled. [10] The results depicted that ketobemidone consumption was significantly lower when patients controlled anesthetic through IP. This led to the patients being able to be discharged earlier than when anesthesia was administered continuously. These findings could be advanced by studying how the route of injection affects the organs in the peritoneal cavity.

In another Phase I clinical trial, patients with ovarian cancer were injected intraperitoneally with dl1520 in order to study the effects of a replication-competent/-selective virus. [11] The effects of this study were the onset of flu-like symptoms, emesis, and abdominal pain. The study overall defines appropriate doses and toxicity levels of dl1520 when injected intraperitoneally.

One study attempted to diagnose hepatic hydrothorax with the use of injecting Sonazoid intraperitoneally. Sonazoid was utilized to aid with contrast-enhanced ultrasonography by enhancing the peritoneal and pleural cavities. [12] This study demonstrates how intraperitoneal injections can be used to help diagnose diseases by providing direct access to the peritoneal cavity and affecting the organs in the cavity.

In a case of a ruptured hepatocellular carcinoma, it was reported that the patient was treated successfully through the use of an intraperitoneal injection of OK-432, which is an immunomodulatory agent. [13] The patient was a 51-year-old male who was hospitalized. The delivery of OK-432 occurred a total of four times in a span of one week. The results of this IP injection were the disappearance of the ascites associated with the rupture. This case is a good example of how IP injections can be used to deliver a drug that can help to treat or cure a medical diagnosis over the use of other routes of delivery. The results set a precedent of how other drugs may be delivered in this way to treat other similar medical issues after further research.

In 2018, a patient with stage IV ovarian cancer and peritoneal metastases was injected intraperitoneally with 12g of mixed cannabinoid before later being hospitalized. [14] The symptoms of this included impairment of cognitive and psychomotor abilities. Because of the injection of cannabis, the patient was predicted to have some level of THC in the blood from absorption. This case presents the question of how THC is absorbed in the peritoneal cavity. It also shows how easily substances are absorbed through the peritoneal cavity after an IP injection.

Overall, this section provides a few examples of the effects and uses of intraperitoneal injections in human patients. There are a variety of uses and possibilities for many more in the future with further research and approval.

Use in Non-Human Animals

When searching "intraperitoneal injections" a majority of the results relate to the use of IP injections in murine or rat models in order to study the effect of some drug or chemical. Intraperitoneal injections are the preferred method of administration in many experimental studies due to the quick onset of effects post injection. This allows researchers to observe the effects of a drug in a shorter period of time, and allows them to study the effects of drugs on multiple organs that are in the peritoneal cavity at once. In order to effectively administer drugs through IP injections, the stomach of the animal is exposed, and the injection is given in the lower abdomen. The most efficient method to inject small animals is a two-person method where one holds the rodent and the other person injects the rodent at about 10 to 20 degrees in mice and 20 to 45 degrees in rats. The holder retains the arms of the animal and tilts the head lower than the abdomen to create optimal space in the peritoneal cavity. [2]

There has been some debate on whether intraperitoneal injections are the best route of administration for experimental animal studies. It was concluded in a review article that utilizing IP injections to administer drugs to laboratory rodents in experimental studies is acceptable when being applied to proof-of-concept studies. [15]

A study was conducted to determine the best route of administration to transplant mesenchymal stem cells for colitis. This study compared intraperitoneal injections, intravenous injections, and anal injections. It was concluded that the intraperitoneal injection had the highest survival rate of 87.5%. [16] This study shows how intraperitoneal injections can be more effective and beneficial than other traditional routes of administration.

One article reviews the injection of sodium pentobarbital to euthanize rodents intraperitoneally. [2] Killing the rodent through an intraperitoneal route was originally recommended over other routes such as inhalants because it was thought to be more efficient and ethical. The article overviews whether IP is the best option for euthanization based on evidence associated with welfare implications. It was concluded that there is evidence that IP may not be the best method of euthenasia due to possibilities of missinjection.

Another example of how intraperitoneal injections are used in studies involving rodents is the use of IP for micro-CT contrast enhanced detection of liver tumors. [17] Contrast agents were administered intraperitoneally instead of intravenously to avoid errors and challenges. It was determined that IP injections are a good option for Fenestra to quantify liver tumors in mice.

An example of how intraperitoneal injections can be optimized is depicted in a study where IP injections are used to deliver anesthesia to mice. This study goes over the dosages, adverse effects, and more of using intraperitoneal injections of anesthesia. [18]

An example of when intraperitoneal injections are not ideal is given in a study where the best route of administration was determined for cancer biotherapy. [19] It was concluded that IP administration should not be used over intravenous therapy due to high radiation absorption in the intestines. This shows an important limitation to the use of IP therapy.

The provided examples show a variety of uses for intraperitoneal injections in animals for in vitro studies. Some of the examples depict situations where IP injections are not ideal, while others prove the advantageous uses if this delivery method. Overall, many studies utilize IP injections to deliver therapeutics to lab animals due to the efficiency of the administration route.

Current Drugs Delivered Intraperitoneally

Currently, there are a handful of drugs that are delivered through intraperitoneal injection for chemotherapy. They are mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluorouracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed, and melphalan. [20] There needs to be more research done to determine appropriate dosing and combinations of these drugs to advance intraperitoneal drug delivery.

Related Research Articles

General anaesthetics are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of awareness to painful stimuli, sufficient to facilitate surgical applications in clinical and veterinary practice. General anaesthetics do not act as analgesics and should also not be confused with sedatives. General anaesthetics are a structurally diverse group of compounds whose mechanisms encompasses multiple biological targets involved in the control of neuronal pathways. The precise workings are the subject of some debate and ongoing research.

<span class="mw-page-title-main">Local anesthetic</span> Medications to reversibly block pain

A local anesthetic (LA) is a medication that causes absence of all sensation in a specific body part without loss of consciousness, as opposed to a general anesthetic, which eliminates all sensation in the entire body and causes unconsciousness. Local anesthetics are most commonly used to eliminate pain during or after surgery. When it is used on specific nerve pathways, paralysis also can be induced.

<span class="mw-page-title-main">Intravenous therapy</span> Medication administered into a vein

Intravenous therapy is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water by mouth. It may also be used to administer medications or other medical therapy such as blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use.

<span class="mw-page-title-main">Lidocaine</span> Local anesthetic

Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidocaine typically begins working within several minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding.

<span class="mw-page-title-main">Hypodermic needle</span> Device to inject substances into the circulatory system

A hypodermic needle, one of a category of medical tools which enter the skin, called sharps, is a very thin, hollow tube with one sharp tip. It is commonly used with a syringe, a hand-operated device with a plunger, to inject substances into the body or extract fluids from the body. Large-bore hypodermic intervention is especially useful in catastrophic blood loss or treating shock.

<span class="mw-page-title-main">Route of administration</span> Path by which a drug, fluid, poison, or other substance is taken into the body

In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body.

<span class="mw-page-title-main">Subcutaneous administration</span> Insertion of medication under the skin

Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion.

Animal euthanasia is the act of killing an animal humanely, most commonly with injectable drugs. Reasons for euthanasia include incurable conditions or diseases, lack of resources to continue supporting the animal, or laboratory test procedures. Euthanasia methods are designed to cause minimal pain and distress. Euthanasia is distinct from animal slaughter and pest control.

<span class="mw-page-title-main">Injection (medicine)</span> Method of medication administration

An injection is the act of administering a liquid, especially a drug, into a person's body using a needle and a syringe. An injection is considered a form of parenteral drug administration; it does not involve absorption in the digestive tract. This allows the medication to be absorbed more rapidly and avoid the first pass effect. There are many types of injection, which are generally named after the body tissue the injection is administered into. This includes common injections such as subcutaneous, intramuscular, and intravenous injections, as well as less common injections such as intraperitoneal, intraosseous, intracardiac, intraarticular, and intracavernous injections.

<span class="mw-page-title-main">Laboratory mouse</span> Mouse used for scientific research

The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory mice are usually of the species Mus musculus. They are the most commonly used mammalian research model and are used for research in genetics, physiology, psychology, medicine and other scientific disciplines. Mice belong to the Euarchontoglires clade, which includes humans. This close relationship, the associated high homology with humans, their ease of maintenance and handling, and their high reproduction rate, make mice particularly suitable models for human-oriented research. The laboratory mouse genome has been sequenced and many mouse genes have human homologues. Lab mice sold at pet stores for snake food can also be kept as pets.

<span class="mw-page-title-main">Xylazine</span> Veterinary anesthetic, sedative and analgesic

Xylazine is a drug used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle, and other non-human mammals. It is an analog of clonidine and an agonist at the α2 class of adrenergic receptor.

Palifermin is a truncated human recombinant keratinocyte growth factor (KGF) produced in Escherichia coli. KGF stimulates the growth of cells that line the surface of the mouth and intestinal tract.

Dosage forms are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration, and apportioned into a particular dose. For example, two products may both be amoxicillin, but one is in 500 mg capsules and another is in 250 mg chewable tablets. The term unit dose can also sometimes encompass non-reusable packaging as well, although the FDA distinguishes that by unit-dose "packaging" or "dispensing". Depending on the context, multi(ple) unit dose can refer to distinct drug products packaged together, or to a single drug product containing multiple drugs and/or doses. The term dosage form can also sometimes refer only to the pharmaceutical formulation of a drug product's constituent drug substance(s) and any blends involved, without considering matters beyond that. Because of the somewhat vague boundaries and unclear overlap of these terms and certain variants and qualifiers within the pharmaceutical industry, caution is often advisable when conversing with someone who may be unfamiliar with another person's use of the term.

<span class="mw-page-title-main">Hyperthermic intraperitoneal chemotherapy</span>

Intraperitoneal hyperthermic chemoperfusion is a type of hyperthermia therapy used in combination with surgery in the treatment of advanced abdominal cancers. In this procedure, warmed anti-cancer medications are infused and circulated in the peritoneal cavity (abdomen) for a short period of time. The chemotherapeutic agents generally infused during IPHC are mitomycin-C and cisplatin.

Directed enzyme prodrug therapy (DEPT) uses enzymes artificially introduced into the body to convert prodrugs, which have no or poor biologically activity, to the active form in the desired location within the body. Many chemotherapy drugs for cancer lack tumour specificity and the doses required to reach therapeutic levels in the tumour are often toxic to other tissues. DEPT strategies are an experimental method of reducing the systemic toxicity of a drug, by achieving high levels of the active drug only at the desired site. This article describes the variations of DEPT technology.

Cytoreductive surgery (CRS) is a surgical procedure that aims to reduce the amount of cancer cells in the abdominal cavity for patients with tumors that have spread intraabdominally. It is often used to treat ovarian cancer but can also be used for other abdominal malignancies.

GL-ONC1 is an investigational therapeutic product consisting of the clinical grade formulation of the laboratory strain GLV-1h68, an oncolytic virus developed by Genelux Corporation. GL-ONC1 is currently under evaluation in Phase I/II human clinical trials in the United States and Europe.

<span class="mw-page-title-main">Intracerebroventricular injection</span> Injection into the cerebrospinal fluid

Intracerebroventricular injection is a route of administration for drugs via injection into the cerebral ventricles so that it reaches the cerebrospinal fluid (CSF). This route of administration is often used to bypass the blood-brain barrier because it can prevent important medications from reaching the central nervous system. This injection method is widely used in diseased mice models to study the effect of drugs, plasmid DNA, and viral vectors on the central nervous system. In humans, ICV injection can be used for the administration of drugs for various reasons. Examples include the treatment of Spinal Muscular Atrophy (SMA), the administration of chemotherapy in gliomas, and the administration of drugs for long-term pain management. ICV injection is also used in the creation of diseased animal models specifically to model neurological disorders.

Ovarian germ cell tumors (OGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad, which accounts for about 2.6% of all ovarian malignancies. There are four main types of OGCTs, namely dysgerminomas, yolk sac tumor, teratoma, and choriocarcinoma.

<span class="mw-page-title-main">Euthanasia solution</span>

A euthanasia solution is a drug-containing aqueous solution for intentionally ending life to either relieve pain and suffering or execute convicts. The drugs used in euthanasia solution do not only need to be safe to personnel, but they also need to have a rapid onset of action and minimize the possible pain felt by humans and animals. To satisfy these requirements, the active ingredients in the euthanasia solution are usually anaesthetics, respiratory depressants, cardiotoxic drugs and cytotoxic drugs.

References

  1. Swart AM, Burdett S, Ledermann J, Mook P, Parmar MK (April 2008). "Why i.p. therapy cannot yet be considered as a standard of care for the first-line treatment of ovarian cancer: a systematic review". Ann. Oncol. 19 (4): 688–95. doi: 10.1093/annonc/mdm518 . PMID   18006894.
  2. 1 2 3 Laferriere, C.A.; Pang, D.S. (2020). "Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents". Journal of the American Association for Laboratory Animal Science. 59 (3): 254–263. doi:10.30802/AALAS-JAALAS-19-000081. PMC   7210732 . PMID   32156325.
  3. Rowlands, I.W. (1957). "Insemination of the Guinea-pig by Intraperitoneal Injection". Journal of Endocrinology. 16 (1): 98–106. doi:10.1677/joe.0.0160098. PMID   13491738.
  4. Straus, Werner (1957). "Changes in "droplet" fractions from rat kidney cells after intraperitoneal injection of egg white". J Biophys Biochem Cytol. 3 (6): 933–947. doi:10.1083/jcb.3.6.933. PMC   2224142 . PMID   13481027.
  5. Whittle, Brian A. (1964). "Release of a kinin by intraperitoneal injection of chemical agents in mice". International Journal of Neuropharmacology. 3 (4): 369–IN1. doi:10.1016/0028-3908(64)90066-8. PMID   14334868.
  6. Hamburg, M.D. (1967). "Retrograde Amnesia Produced by Intraperitoneal Injection of Physostigmine". Science. 156 (3777): 973–974. Bibcode:1967Sci...156..973H. doi:10.1126/science.156.3777.973. PMID   6067162. S2CID   46029262.
  7. Anton-Tay, F.; Chou, C.; Anton, S.; Wurtman, R.J. (1968). "Brain Serotonin Concentration: Elevation Following Intraperitoneal Administration of Melatonin". Science. 162 (3850): 277–278. Bibcode:1968Sci...162..277A. doi:10.1126/science.162.3850.277. JSTOR   1725071. PMID   5675470. S2CID   6484761.
  8. Arioli, V.; Rossi, E. (1969). "Errors Related to Different Techniques of Intraperitoneal Injection in Mice". Applied Microbiology. 19 (4): 704–705. doi:10.1128/am.19.4.704-705.1970. PMC   376768 . PMID   5418953. S2CID   237231042.
  9. Sturman, J A; Dawkins, P D; McArthur, N; Smith, M J H (1968). "The distribution of salicylate in mouse tissues after intraperitoneal injection". Journal of Pharmacy and Pharmacology. 20 (1): 58–63. doi:10.1111/j.2042-7158.1968.tb09619.x. PMID   4384147. S2CID   41866123.
  10. Perniola, A (2014). "Postoperative pain after abdominal hysterectomy: a randomized, double-blind, controlled trial comparing continuous infusion vs patient-controlled intraperitoneal injection of local anaesthetic". British Journal of Anaesthesia. 112 (2): 328–336. doi: 10.1093/bja/aet345 . PMID   24185607.
  11. Vasey PA, Shulman LN, Campos S, Davis J, Gore M, Johnston S, Kirn DH, O'Neill V, Siddiqui N, Seiden MV, Kaye SB (15 March 2002). "Phase I Trial of Intraperitoneal Injection of the E1B-55-kd-Gene–Deleted Adenovirus ONYX-015 (dl1520) Given on Days 1 Through 5 Every 3 Weeks in Patients With Recurrent/Refractory Epithelial Ovarian Cancer". J Clin Oncol. 20 (6): 1562–1569. doi:10.1200/JCO.2002.20.6.1562. PMID   11896105.
  12. Tamano, M. (2010). "Diagnosis of hepatic hydrothorax using contrast-enhanced ultrasonography with intraperitoneal injection of Sonazoid". Journal of Gastroenterology and Hepatology. 25 (2): 383–386. doi:10.1111/j.1440-1746.2009.06002.x. PMID   19817961. S2CID   10043091.
  13. Shiratori, M. (2004). "Successful treatment of ruptured hepatocellular carcinoma with intraperitoneal injection of OK-432". Journal of Hepato-Biliary-Pancreatic Surgery. 11 (6): 426–429. doi:10.1007/s00534-004-0921-8. PMID   15619020.
  14. Lucas, C.J.; Galettis, P.; Song, S.; Solowij, N.; Reuter, S.E.; Schneider, J.; Martin, J.H. (2018). "Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer". Clinical Therapeutics. 40 (9): 1442–1447. doi: 10.1016/j.clinthera.2017.12.008 . PMID   29317112. S2CID   41474813.
  15. Al Shoyaib, A.; Archie, S.R.; Karamyan, V.T. (2020). "Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies?". Pharm Res. 37 (12): 12. doi:10.1007/s11095-019-2745-x. PMC   7412579 . PMID   31873819.
  16. Wang, M.; Liang, C.; Hu, H. (2016). "Intraperitoneal injection (IP), Intravenous injection (IV) or anal injection (AI)? Best way for mesenchymal stem cells transplantation for colitis". Sci Rep. 6 (30696): 30696. Bibcode:2016NatSR...630696W. doi:10.1038/srep30696. PMC   4973258 . PMID   27488951.
  17. Sweeney, N.; Marchant, S.; Martinez, J.D. (2019). "Intraperitoneal injections as an alternative method for micro-CT contrast enhanced detection of murine liver tumors". BioTechniques. 66 (5): 214–217. doi: 10.2144/btn-2018-0162 . PMID   31050302. S2CID   143433447.
  18. Arras, M.; Autenried, P.; Rettich, A.; Spaeni, D.; Rulicke, T. (2001). "Optimization of Intraperitoneal Injection Anesthesia in Mice: Drugs, Dosages, Adverse Effects, and Anesthesia Depth". Comparative Medicine. 51 (5): 443–456. PMID   11924805.
  19. Dou, Shuping; Smith, Miles; Wang, Yuzhen; Rusckowski, Mary; Liu, Guozheng (May 2013). "Intraperitoneal Injection Is Not Always a Suitable Alternative to Intravenous Injection for Radiotherapy". Cancer Biotherapy and Radiopharmaceuticals. 28 (4): 335–342. doi:10.1089/cbr.2012.1351. PMC   3653381 . PMID   23469942.
  20. Bree, Eelco de; Michelakis, Dimosthenis; Stamatiou, Dimitris; Romanos, John; Zoras, Odysseas (1 June 2017). "Pharmacological principles of intraperitoneal and bidirectional chemotherapy". Pleura and Peritoneum. 2 (2): 47–62. doi:10.1515/pp-2017-0010. PMC   6405033 . PMID   30911633. S2CID   79678140.