Hemoperitoneum , probably due to anticoagulant therapy with warfarin in a patient undergoing PD
Hemoperitoneum has a wide differential diagnosis (Table 17.1). Menstruation is a common and benign cause of blood in the peritoneal cavity. In a recent review of hemoperitoneum, bleeding due to menstruation was the most common cause, accounting for one third of the benign episodes of hemoperitoneum (Greenberg et al. 1992). The majority of regularly menstruating women undergoing PD experience repeated hemoperitoneum.
Causes of hemoperitoneum in peritoneal dialysis
Hashim et al. (1964)
Bleeding ovarian cysts
Renal cell carcinoma
Suzuki et al. (2005)
Adenocarcinoma of the colon
Suzuki et al. (2005)
Polycystic kidney disease
Yamamoto et al. (2010)
Idiopathic thrombopenic purpura
Peritoneal membrane disease
Yoshimoto et al. (1993)
Radiation-induced peritoneal fibrosis
Yoshimoto et al. (1998)
Catheter-induced splenic rupture
Nace et al. (1985)
Leakage from extra-peritoneal hematoma
Greenberg et al. (1992)
Blumenkrantz et al. (1981)
There are two mechanisms by which menstruation can lead to hemoperitoneum in patients receiving PD. If endometrial tissue is present in the peritoneal cavity, it will shed simultaneously with the intrauterine endometrium, and bloody dialysate will occur simultaneously with the menstrual flow. The other mechanism is that the shed uterine tissue and blood move out of both the uterine cervix and in a retrograde manner through the fallopian tubes into the peritoneal cavity. The peritoneal bleeding may start a few days prior to the appearance of blood in the vagina (Blumenkrantz et al. 1981). It has been suggested that the timing of menstrual pain matches the appearance of peritoneal blood rather than the vaginal menstrual flow; thus, peritoneal blood may be an important cause of dysmenorrhea (Blumenkrantz et al. 1981).
Women of reproductive age may also experience hemoperitoneum coincident with ovulation (Greenberg et al. 1992; Harnett et al. 1987). It is suggested that the source of blood is bleeding from the ovary, which occurs with the rupture and release of the ovum. Other ovarian sources of bleeding include ruptured cysts with sufficient to bleeding to necessitate transfusion (Fraley et al. 1988). The episodes of hemoperitoneum associated with menstruation and ovulation are recognized by their periodicity and occurrence in women of reproductive age. While this cause of blood in the dialysate is considered benign, there are potential complications. The blood loss can exacerbate anemia due to chronic kidney disease, and for this reason alone anovulant therapy may be indicated.
A reported association between hemoperitoneum and Staphylococcus epidermidis peritonitis suggests that the bloody dialysate may provide a rich growth medium for intraperitoneal bacteria. Other investigators, however, have been unable to document an increased frequency of peritonitis in relation to menstruation-generated hemoperitoneum (Greenberg et al. 1992).
In non-menstruating patients, hemoperitoneum must be carefully investigated. There are a number of surgical causes of blood in the peritoneal cavity, including cholecystitis (Nace et al. 1985), rupture of the spleen (de los Santos et al. 1986), and pancreatitis (Greenberg et al. 1992). In these cases, it should be apparent that the patient has a painful abdomen, and localized tenderness in association with bloody effluent requires an urgent surgical consultation. Hemoperitoneum due to splenic rupture, which occurs in association with PD, is very unusual. However, hemoperitoneum due to a ruptured spleen has been reported in chronic leukemia patients undergoing PD (Wang et al. 1998).
In non-dialysis patients there may be episodes of peritoneal bleeding that never come to medical attention because they are not observed. Peritoneal dialysis patients, on the other hand, have a window into the peritoneal cavity and otherwise asymptomatic peritoneal bleeding is readily apparent. This explains the hemoperitoneum that is observed following colonoscopy (Nace et al. 1985; Greenberg et al. 1992), in patients with coagulation disorders (Greenberg et al. 1992), polycystic kidney disease (PKD) (Blake and Abraham 1988), in patients with leakage from a hematoma outside the peritoneal cavity (Greenberg et al. 1992), and following extracorporeal lithotripsy for kidney stones (Husserl and Tapia 1987).
In patients with PKD, bleeding into a cyst can be associated with hematuria or hemoperitoneum (Blake and Abraham 1988). A case of bloody effluent in a PKD patient receiving PD was described. In this case, however, the bleeding was painless, which would be unusual if a kidney cyst had ruptured into the peritoneal cavity. Moreover, leukocytosis was observed in the dialysis effluent. These unusual features led to further investigations, which revealed that the patient had renal cell carcinoma (Twardowski et al. 1992). Bloody dialysate has also been mentioned in association with adenocarcinoma of the colon (Twardowski et al. 1992), presumably from the serosal spread of the tumor.
Recurrent hemoperitoneum may be a forerunner of peritoneal membrane disease. Bloody effluent has been described in association with hyperparathyroidism in patients with peritoneal calcification (Francis et al. 1990), in patients with radiation-induced peritoneal injury (Hassell et al. 1984), and as the presenting abnormality in patients who develop sclerosing peritonitis (Greenberg et al. 1992).
In patients with hemoperitoneum , there is a risk of the intraperitoneal blood coagulating in the catheter lumen. Thus, it has been recommended that intraperitoneal heparin (500–1000 U/L) be administered for as long as the dialysate still has visible blood or fibrin. In the clinical setting, intraperitoneal heparin does not worsen the bleeding or lead to systemic anticoagulation . In some instances of hemoperitoneum, the use of rapid exchanges with dialysate at room temperature leads to the rapid resolution of the bleeding . It is hypothesized that the relatively cool dialysate induces peritoneal vasoconstriction and that this leads to hemostasis (Goodkin and Benning 1990).
The risk of abdominal hernia is significantly higher in peritoneal dialysis (PD) patients than it is in hemodialysis patients (Fig. 17.2) (Lee et al. 2015). The presence of dialysis fluid in the peritoneal cavity leads to increased intra-abdominal pressure (IAP). Pressure within the abdomen increases in proportion to the volume of dialysate that is instilled (Twardowski et al. 1986). The supine patient generates the lowest IAP for a given volume of peritoneal fluid, while coughing in the sitting and upright positions results in the greatest pressure. In addition, a given activity can generate higher IAPs in patients who are older or more obese (Twardowski et al. 1986). A recent study in a small modern cohort examined the outcomes of large (in size) PD patients. However, it demonstrated that hernias and leaks were more common in patients weighing less than 90 kg than they were in obese patients (Ananthakrishnan et al. 2014). Another report demonstrated that the frequency of hernia in childhood PD patients was 8.6% (Kim et al. 2015a).
A CT scan of indirect inguinal hernia exhibiting peritoneal fluid connecting the peritoneal cavity with the testis in a PD patient (coronal plane)
In accordance with Laplace’s law, tension on the abdominal wall increases with the instillation of dialysate, as a result of the increase in IAP. An increase in the abdominal pressure and abdominal wall tension may lead to the formation of hernias in patients with congenital or acquired defects in or around the abdomen. Areas of weakness are very important in the pathogenesis of hernias. Indeed, the IAP in hernia patients is no different from the IAP in patients without hernias (Durand et al. 1992). The causes of hernias in PD patients have been described (Table 17.2). The most common types of hernia are incisional or occur through the catheter placement site (Digenis et al. 1982; O’Connor et al. 1986); other studies have reported that inguinal (Kauffman and Adams 1986) or umbilical (Wetherington et al. 1985) hernias occur most frequently. Asymptomatic hernias are probably quite common and may not be detected until a complication, such as bowel strangulation, occurs. A review found that 11.5% of PD patients developed a hernia over 5 years of follow-up. Patients with hernias tend to be older, female, and multiparous. They also tend to experience a higher frequency of postoperative leak at the time of catheter insertion (Digenis et al. 1982) and to have undergone a previous hernia repair (O’Connor et al. 1986).
Hernia in patients on peritoneal dialysis
Catheter incision site
Fraley et al. (1988)
de los Santos et al. (1986)
Harnett et al. (1987)
Foramen of Morgagni
Twardowski et al. (1992)
Harnett et al. (1987)
Patients with polycystic kidney disease (PKD) may be predisposed to hernia formation, either as a result of the higher IAP caused by large kidneys or as a manifestation of a generalized collagen disorder (Modi et al. 1989). The mean time for the development of a hernia is 1 year, and the risk increases by 20% for each year that a patient is on PD (O’Connor et al. 1986).
A major potential area of weakness is the abdominal incision for the implantation of the dialysis catheter . When this incision is made in the midline, there is a predilection for an incisional hernia to develop because this is an anatomically weak area (Apostolidis et al. 1988). Changing to a paramedian incision through the rectus muscle is associated with rates of perioperative leak and hernia formation (Spence et al. 1985).
Another area of potential weakness for herniation is the processus vaginalis. After the migration of the testis in fetal life, the processus vaginalis normally undergoes obliteration. In many cases, however, this does not occur, and the increased abdominal pressure during PD may push the bowel into the processus vaginalis, resulting in an indirect inguinal hernia. Male pediatric patients may be predisposed to this complication. If they develop a unilateral inguinal hernia, both sides should probably be prophylactically repaired (Khoury et al. 1991).
Most hernias present as a painless swelling (Digenis et al. 1982). The bowel has been reported to herniate through the diaphragm at the foramen of Morgagni and to present as a retrosternal air-fluid level (Ramos et al. 1982). The most troublesome complications are incarceration and strangulation of bowel. This can occur through almost any kind of hernia, but especially small ones. It may present as a tender lump (Power et al. 1981), recurrent gram-negative peritonitis , bowel obstruction, or perforation (Digenis et al. 1982). Bowel incarceration or strangulation can mimic peritonitis (Power et al. 1981), and this complication must be kept in mind, particularly if the site of herniation is not obvious.
Hernias deserve surgical repair. Although large ventral hernias carry little measurable risk of bowel incarceration (Moffat et al. 1982), they are unsightly and prone to becoming enlarged. The other types of hernias should be repaired because of the risk of bowel incarceration and strangulation. After surgery , the patient can be temporarily maintained on low volume intermittent PD to allow time for wound healing. If hernias recur, other options include changing the patient to nighttime cycler dialysis, where dialysis is performed with the patient in the supine position, under a lower IAP, or with lower volumes of dialysate but more frequent exchanges.
Increased intra-abdominal pressure can result in the leakage of dialysis fluid across the diaphragm and into the pleural space. The accumulation of dialysis fluid in the pleural cavity is called hydrothorax. Hydrothorax commonly presents on the right side in peritoneal dialysis (PD) patients (Fig. 17.3) (Saha and Singh 2007). It is not clear how often hydrothorax occurs in patients receiving PD, but most studies estimate that the incidence is less than 5%, which would make it a less frequent consequence of an increased IAP than abdominal hernia (Maher and Schreiner 1965; Nomoto et al. 1989). However, it is possible that hydrothorax occurs more frequently but does not come to medical attention if the patient is asymptomatic or if minor complaints of shortness of breath are overlooked.
A chest X-ray film showing moderate pleural effusion on the right side in a PD patient
A defect in the diaphragm must be present to allow the flux of dialysis fluid from the peritoneal cavity into the pleural cavity. Autopsy studies have revealed the localized absence of muscle fibers in the hemidiaphragm (Lieberman et al. 1966). The missing muscle fibers are replaced with a disordered network of collagen. One or more defects in the tendinous part of the hemidiaphragm have been observed (Lieberman et al. 1966).
In pediatric patients receiving PD who develop hydrothorax, diaphragmatic eventration rather than hernia has been described at surgery (Bjerke et al. 1991).
It is likely that these defects in the musculotendinous part of the diaphragm are not rare occurrences. Rather, they may only come to medical attention when there is fluid in the abdominal cavity under increased pressure in a manner similar to patent processus vaginalis. This explains why hydrothorax has been described in patients receiving PD and in those with liver disease or with ovarian cancer and ascites.
The extent of the deficiency in the hemidiaphragm varies among patients. Patients with a clear preexisting connection between the peritoneal cavity and the pleural space are probably the same patients who develop hydrothorax with their first-ever infusion of dialysis fluid. In contrast, some patients develop hydrothorax months to years after the start of PD. Presumably, those patients have attenuated tissue separating the pleural space from the peritoneal cavity, and it may take repeated exposure to an increased IAP or an episode of peritonitis to remove the barrier between the two cavities.
Small pleural effusions can be asymptomatic and are detected by routine chest radiography. Larger pleural effusions can lead to respiratory embarrassment.
The shortness of breath that results from pleural effusion can be mistaken for congestive heart failure . The patient may choose more hypertonic dialysis solutions in an effort to increase ultrafiltration . In patients with hydrothorax, however, increased ultrafiltration will lead to an even greater IAP with further flux of the dialysate into the pleural space, worsening the symptoms. Thus, a history of complaints of dyspnea that appears to worsen with hypertonic dialysate should suggest the possibility of hydrothorax, particularly if the volume of effluent that returns is less than normal. On physical examination, the absence of breath sounds and stony dullness to percussion in the lung base is consistent with pleural effusion. There are few reports on tension hydrothorax (Rossoff 1990).
Chest X-ray shows pleural effusion, which occurs on the right side in most patients. It is assumed that the diaphragm defect occurs more frequently on the right side; however, the reason for this is unknown. Alternatively, the heart may cover any defects that might be present in the left hemidiaphragm.
Clearly, other causes of pleural effusion should be ruled out, including local parenchymal lung disease, congestive heart failure , and pleuritis. The scenario wherein a patient develops a large right-sided pleural effusion within the first few dialysis sessions is strongly suggestive of hydrothorax. However, when a patient on PD for months develops peritonitis , fluid overload , and pleural effusion, it can be more difficult to make the correct diagnosis.
Thoracentesis can be helpful for making a correct diagnosis in patients in whom the etiology of pleural effusion is uncertain. If the pleural effusion is composed of dialysate, the glucose concentration is very high (usually >40 mmol/L), and the fluid has a low protein concentration consistent with a transudate.
Even when the diagnosis is certain, thoracentesis should be performed for patients who are short of breath from hydrothorax. The evacuation of one or more liters of fluid can be expected to lead to a significant improvement in the patients’ respiratory status.
In the absence of thoracentesis, the presence of peritoneal-pleural communication can be confirmed by isotopic scanning. Between 3 and 10 mCi of technetium-labeled macroaggregated albumin or sulfur colloid is instilled into the peritoneal cavity along with the usual volume of dialysis fluid. The patient should move around to ensure the mixing of the radioisotope and dialysate and to increase the IAP. Subsequent scanning detects the movement of the isotope above the hemidiaphragm. Although this usually is detectable in the first few minutes, sometimes late pictures (up to 6 h) need to be taken. This method is convenient but is not completely foolproof. Defects have been found in the diaphragm at surgery in patients in whom isotopic scanning was negative (Mestas et al. 1991).
Thoracentesis is recommended for the immediate treatment of hydrothorax if respiratory compromise is present. Otherwise, the discontinuation of PD often leads to the rapid and dramatic resolution of pleural effusion (Nomoto et al. 1989). In a small number of patients, the effusion is very slow to resolve, suggesting the possibility of one-way or ball-valve type communication between the peritoneal and pleural spaces. In such cases, thoracentesis may be helpful for hastening the resolution of the pleural effusion.
Subsequent treatment depends on whether the patient is going to continue on PD. The occurrence of hydrothorax is occasionally so distressing to the patient that the patient requests a transfer to hemodialysis. In this case, the communication between the peritoneal cavity and the pleural space should be of no consequence, and nothing further needs to be done after the resolution of effusion.
If the patient is going to continue PD, there are several different options.
Temporary hemodialysis (2–4 weeks) with a subsequent return to PD: There may be a transient loss of the integrity of the cell layers overlying a diaphragmatic defect, especially in the presence of peritonitis . If PD is temporarily discontinued and the mesothelium is allowed to reconstitute itself over the defect, it is possible that the peritoneo-pleural communication may become resealed. It is less likely that this would be effective in patients demonstrating pleural leak at the first dialysis session; however, this phenomenon has even been reported after a 2-month hiatus from hemodialysis. It has been suggested that the dialysate in the pleural space may act as a sclerosing agent and prevent subsequent leaks (Rutland and Kalowski 1992).
Temporary hemodialysis with a return to a PD regimen with lower intra-abdominal pressure: Patients who experience hydrothorax on PD are sometimes able to resume PD using a cycler. Even though the supine position might be thought to be conducive to the movement of fluid into the pleural cavity, the reduction in IAP afforded by this posture seems to more than compensate for possibility (Townsend and Fragola 1982). The use of smaller dialysis volumes with more frequent exchanges is helpful in minimizing the increase in IAP.
The obliteration of the pleural space: Previous studies have reported the successful obliteration of the pleural cavity. In this case, the leaves of the pleura stick together and prevent the re-accumulation of pleural fluid. Different agents can be used to induce the obliteration of the pleural space. Oxytetracycline (20 mg/kg) has been administered via a thoracostomy tube (Nomoto et al. 1989; Benz and Schleifer 1985). It is important that the patient remains supine for up to 24 h and assumes different positions, including head down, to ensure that all of the pleural surfaces are exposed to the agent. The patient should also receive analgesia, as this procedure can be painful. Talc has also been successfully applied for the obliteration of the pleural cavity in a PD (Posen and Sachs 1979). The obliteration of the pleural cavity has also been accomplished by the instillation of 40 mL of autologous blood. The patient should be maintained, if possible, on hemodialysis for a few weeks to allow the obliteration of the pleural cavity to take place. More than one instillation of blood may be necessary, but the benefit of the blood is that it appears to be a relatively painless procedure in comparison to the use of talc or tetracycline (Hidai et al. 1989). There are reports from Japan of the use of OK-432, a hemolytic streptococcal preparation, and the use of Nocardia rubra cell wall skeleton to obliterate the pleural cavity (Nomoto et al. 1989). Finally, the instillation of a combination of aprotinin-calciumchloride-thrombin and fibrin glue in the drained pleural cavity was reported to have successfully prevented recurrent hydrothorax in a patient in whom treatment with other agents had been unsuccessful (Vlachojannis et al. 1985).
Operative repair: At thoracotomy, communication between the peritoneal cavity and the pleural space may be visualized. Sometimes blebs or blisters are quickly recognized and can be sutured and reinforced with Teflon felt patches. It is recommended that two to three liters of dialysate be infused into the peritoneal cavity through the dialysis catheter . The diaphragm is inspected from the pleural side to check for the seepage of dialysate through holes or blisters. It is important that the surgeon be patient as it may take time for seepage to be recognized (Allen and Matthews 1991). In the case of eventration of the diaphragm, as reported in the pediatric literature, plication with nonabsorbable sutures can be an effective surgical repair. These patients are able to return to PD (Bjerke et al. 1991).
In summary, hydrothorax is a well-described but relatively uncommon complication of PD. The diagnosis is relatively simple once the possibility of peritoneal-pleural communication has been investigated. Thoracentesis may be necessary to confirm the diagnosis and is mandated by respiratory embarrassment. As described above, several treatment options are available if the patient is willing to continue with PD.
17.6 Acid-Base and Electrolyte Disorders
17.6.1 Disorders of Water Metabolism
In patients with end-stage renal disease, the serum sodium concentration depends on the relative amount of salt and water being ingested and the amount of salt and water removed by dialysis. Sodium flux into the peritoneal cavity of peritoneal dialysis (PD) patients is caused by diffusion and convection . Because sodium is sieved by the peritoneal membrane, the fluid entering the peritoneal cavity by osmotically driven flow is hyponatremic, more water than salt flows from plasma to the peritoneal cavity (Ahearn and Nolph 1972). In theory, this flux should leave the patient with a relative water deficit; thus, the patient should become hypernatremic. However, hypertonicity is a powerful stimulant of ADH secretion, which in turn stimulates thirst. The patient then drinks water or some other hypotonic fluid until tonicity is restored. In fact, PD patients may actually demonstrate plasma sodium concentrations that are slightly lower than normal. There are a number of reasons for the relative water excess, including an increased water intake or the low sodium concentration of the dialysis solution (Lindholm et al. 1986). Infants undergoing PD who are fed normal infant formula may be prone to hyponatremia because the amount of sodium lost through ultrafiltration is greater than that gained from the ingestion of formula. Moreover, the proprietary infant formulas have a high water to sodium ratio, leading to water accumulation and hyponatremia (Paulson et al. 1989).
In a recent study, tolvaptan (15 mg daily), a vasopressin type 2 receptor antagonist, was administered to 15 PD patients (Mori et al. 2013). In 11 of 15 patients, the urine volume increased to more than 400 mL daily. A significant increase in diluted urine was observed, as indicated by a reduction in the specific gravity or osmolality of the urine, or both. The urinary excretion of urea nitrogen and sodium was significantly increased. Increases in the renal Kt/V were observed, but the peritoneal Kt/V was unchanged. A significant increase in creatinine clearance was also observed. The data suggest that tolvaptan not only stimulates water diuresis but also natriuresis, without reducing the residual renal function (RRF) in PD patients. Thus, tolvaptan could be a beneficial tool for controlling body fluid and maintaining the RRF in PD patients; however, the long-term effects of this agent are unclear.