Critical alkalosis following intraperitoneal irrigation with sodium bicarbonate in a patient with pseudomyxoma peritonei

Shirasawa, Yumiko; Orita, Hanayo; Ishida, Kazuyoshi; Morimoto, Yasuhiro; Matsumoto, Mishiya; Sakabe, Takefumi

doi:10.1007/s00540-008-0612-8

Cited by 12 publications

(13 citation statements)

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“…Over the years, there have been several reports of experimental use of different mucolytic agents for the disintegration of PMP mucin in situ . Accompanied with these reports, there was also unfavorable side effect that was associated with the use of these agents.…”

Section: Discussionmentioning

confidence: 99%

“…Accompanied with these reports, there was also unfavorable side effect that was associated with the use of these agents. The use of bicarbonate solution in patients caused alkalosis, whereas dextran sulfate and dextran induced hyperglycemia . Hence, currently, no mucolytics are recommended for routine clinical use in PMP.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, any agents that can dissociate the glycosidic as well as the disulfide linkages in the mucin would effectively soften the mucinous mass and with rehydration, enabling easy removal of the mucin from the peritoneal cavity. To date, there is very little investigation into dissolution of PMP mucin, although there are some reports on the usage of bicarbonates, dextrose, dextran sulfate, hyaluronidases and other agents; none of these agents have been clinically recommended.…”

mentioning

confidence: 99%

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A formulation for in situ lysis of mucin secreted in pseudomyxoma peritonei

Pillai

Akhter

Chua

et al. 2013

Intl Journal of Cancer

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Although numerous clinical attempts have been made to disintegrate mucin secreted by pseudomyxoma peritonei (PMP), none are clinically recommended. Through examination of the pharmacologic characteristics of two novel agents, we titrated an optimized combination of bromelain and N-acetyl cysteine (NAC) that demonstrates in vitro and in vivo efficacy in the dissolution of mucinous ascites from PMP. In the in vitro experiments, 1 g of mucin was incubated in varying concentrations of bromelain (0-400 mg/ml) and NAC (0-5%) individually followed by a combination before arriving at a therapeutic combination dose of 300 mg/ml bromelain 1 4% NAC. This established an effective dose of bromelain 300 mg/ml 1 4% NAC at pH 7.0, when tested in a rat model implanted with 3 g of mucin intraperitoneally (IP). IP administration of the drug in a rat model of PMP was shown to result in mucin disintegration within 72 hr with no toxicity observed.Pseudomyxoma peritonei (PMP) is a rare cancer where excessive mucin secreted by the tumor cells accumulates in the peritoneal cavity. 1,2 The tumor cells are primarily of appendiceal origin although disseminated cancers of the colon, rectum, stomach, gall bladder, small intestines, urinary bladder, lungs, breast pancreas and ovary may also contribute to the disease. 3 The mucinous mass that is secreted accumulates in the abdominal cavity and sets up internal pressure on mainly the digestive tract and hence, the disease culminates in death of the patient through nutritional compromise. 4 Treatment involves laparotomy, removal of mucinous mass and cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) that was first initiated by Sugarbaker and Chang. 5 With this treatment, a multiinstitutional study has shown that the median survival rate was 16.3 years and 10 to 15 year survival rate being 50%. 6 The disease is progressive and hence the patient may require several treatments during the course of the disease, which often leave the patient with numerous compromises. 7 If the mucinous mass can be safely solubilized in the abdominal cavity, then it can be removed by less invasive method, i.e., the use of a catheter through a tiny puncture in the abdominal wall. This method would improve the quality of life of the patient, as many of these patients are known to undergo repeat treatment throughout the course of the disease. 8 Mucins, the gel-forming components of mucinous secretions, are large polydisperse macromolecules (1,000 kDa) comprising a number of glycoprotein monomers (100-10,000 kDa). The polymerization of individual glycoprotein units takes place through the formation of glycosidic linkages. The mucin is further cross-linked to each other through the formation of disulfide bonds by oxidation that takes place either enzymatically or through variation in pH. 9,10 The mucins secreted in PMP patients vary in compactness ranging from low (soft), medium to high (very compact) form containing gristly material that may be mainly of cellular origin. In the past, several mucol...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A formulation for in situ lysis of mucin secreted in pseudomyxoma peritonei

Pillai

Akhter

Chua

et al. 2013

Intl Journal of Cancer

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show abstract

“…Intra peritoneal solutions, which differ very much in pH compared with the body fluids may affect the patient adversely [26] and, hence, we decided to optimize the pH of the mixture closer to neutrality (pH ¼ 7.0). Subsequent studies to attenuate the pH to neutrality showed that the mucolytic mixture did not perform well above 6.0.…”

Section: Resultsmentioning

confidence: 99%

“…Other agents that targets DNA, b-actin, or lipids that are found in the entangled mucin mass have also been investigated [24]. To date there is very little work carried out on the dissolution of mucin resulting from PMP, although some have reported to have succeeded with bicarbonates [25,26], dextrose [27], dextran sulphate [28], hyaluronidase [29], and other agents. Due to inter patient variability of PMP mucin composition and compactness, any single method may have limited success on all patients.…”

Section: Introductionmentioning

confidence: 99%