Complications of Peritoneal Dialysis

Abhijit Kontamwar,MDRenal Consultants, Inc

Clinical Assistant Professor of Internal Medicine at NEOUCOM (Northeastern Ohio Universities Colleges

of Medicine and Pharmacy).

Complications

• Infectious

• Non-infectious

Case

• 65 F h/o chronic GN is on CCPD (APD) for 8 months p/w cloudy dialysate fluid. Also c/o diffuse abdominal pain. Denies fever, nausea, vomiting, constipation.

• Vitals: BP 116/78, P 76

• P/E: exit site appears ok, no discharge or erythema. Diffuse abdominal tenderness +

• Diagnosis????

Infectious complications

• Exit – site infection

• Tunnel infection

• Peritonitis: remains significant cause of– Hospitalization– PD failure– Damage to peritoneal membrane– Morbidity and mortality

Causes of transfer to HD among PD patients

28%

17%18%

15%

22%

Infection Catheter

Inadequate dialysis Psychosocial

Others

Mujais et al; Kidney Int Suppl 2006; 70: S21-36

Hospitalization rates for access related infections

0

5

10

15

20

12months

36months

p<0.0001

HD

PD

Chavers et al, J Am Soc Nephrol 18: 952 – 959, 2007

Peritonitis

• Usual presentation is with– Abdominal pain and– Cloudy effluent fluid

• History– Recent break in technique– h/o peritonitis– Recent exit site infection– Diarrhea, constipation

How does bacteria gain entry into peritoneal cavity?

• During catheter connection• Tracking around the catheter around the exit site• Across the bowel wall; diverticulosis• Transvaginal• Rarely hematogenous

– Bacteremia can cause peritoneal seeding and peritonitis

– Peritonitis rarely causes bacteremia– Use antibiotic prophylaxis for anticipated bacteremia

during procedures like dental work, colonoscopy, GU instrumentation

– Drain effluent before colonoscopy or colposcopy

Pathophysiology

• Multiple connection and disconnections from the transfer set

• Presence of non-physiologic fluid in the peritoneal cavity may impair host defenses

• High glucose concentration, low pH and hyperosmolality dilute resident peritoneal macrophage and cytokine levels

• Constant removal of macrophage and cytokines during each exchange

• Alteration of mesothelial cell defense properties over time

Flush before fill

Connect bag to tubing

Drain old effluent

Flush small amount of dialysate through

tubing to drain bag

Infuse rest of fresh dialysate into

peritoneal cavity

Diagnosis

• At least two of the following three features– Peritoneal fluid leucocytosis; >100 cells/mm3

and at least 50% PMNs– Abdominal pain– Positive culture of the dialysis effluent

Specimen collection and processing

• Effluent fluid sent for cell count with differential, culture and gram stain

• Collection of effluent: 50ml of effluent is centrifuged for 15 min followed by re-suspension of sediment in 3-5 ml of sterile saline and inoculation to media

• Dwell time of at least 2 – 4 hours before effluent collection

• If peritoneal cavity is dry, 1L of dialysate infused to dwell for at least 1 – 2 hours

• Peripheral blood cultures usually not necessary

Microbiology

48

15

2 21 1

20

4

7

0

5

10

15

20

25

30

35

40

45

50

G pos G neg single G neg multi G neg/pos Fungal Fungal & Bact No growth Other Unknown

Organism

Friedrich et al, Kidney Int, Oct 1992; 42: 967-974

Microbiology

Mujais, S. Microbiology and outcomes of peritonitis in North America. Kidney Int 2006; 70:S55

Gram +ive organisms• Coag neg Staph:

– most common – secondary to touch contamination– Mild peritonitis, rapidly responsive to abx

• Staph aureus– Frequently associated with catheter infection– More virulent and resistant to abx– Anterior nares reservoir of staph aureus– Nasal carriers possibly at increased risk of exit site infection and

peritonitis• VRE

– Risen dramatically– Also resistant to penicillin and aminoglycosides

• Group B strep– Rare cause, case reports– Can present with severe systemic symptoms including septic shock

Gram –ve organisms

• Non-pseudomonal gram –ve organisms: aasociated with– Touch contamination– Exit-site infection– Trans mural migration from constipation or colitis– Polymicrobial or anaerobic: due to diverticulitis or bowel

perforation

• Pseudomonal peritonitis– Common at some centers where reduction in touch

contamination peritonitis with techniques like flush before fill and prophylactic topical antibiotic

– Difficult to eradicate– Severe infection can damage peritoneal membrane– Can be associated with catheter infection

Treatment • Majority of peritonitis resolve with outpatient antibiotics treatment

alone• Antibiotics with or w/o fibrinolytic agents. Few cases need catheter

removal• In 2005 International Society of Peritoneal Dialysis (ISPD) working

group established a series of peritonitis treatment guidelines• In 2007 systematic review of 36 RCT was performed addressing the

efficacy of abx and other factors– No specific antimicrobial regimen was superior– Intermittent and continuous dosing were largely equivalent– 1st generation cephalosporins and glycopeptides had equivalent efficacy– In cases with suspected catheter infection, simultaneous catheter

removal resulted in treatment success– The trials were limited by small patient number and inconsistent

outcome definitions

Treatment

• Non-antimicrobial measures– Heparin 500 units/L can be used to lyse or prevent fibrin clots

when dialysate remains cloudy– Pain control

• Dwell time– Long dwell exchanges (4-6 hrs) when compared with short

dwells are associated with higher number of functional macrophages

• Membrane properties: changes during peritonitis– Patients may transiently become rapid transporters, thereby

requiring the use of hypertonic glucose or shorter dwells– Alternatively, icodextrin may be helpful

Empiric Therapy

Initiate empiric therapy

Simultaneous gram +ve andgram –ve coverage

For prevention of fibrin occlusion heparin 500 U/L can be used

Gram +ve coverage: 1st generation cephalosporin or vancomycin

Gram –ve coverage: 3rd generation cephalosporin or aminoglycoside

Empiric therapy

• 1st generation cephalosporin: cefazolin or cephalothin• Vancomycin used at centers with high rate of MRSA• 3rd generation cephalosporin: ceftazidime or cefepime• Short term use of aminoglycoside is safe and does not

diminish residual renal function• Aztreonam can be used in cephalosporin allergic

patients• Monotherapy with imipenem/cilastatin is possible. One

study with 102 patients randomly assigned to either imipenem/cilastatin or cefazolin + ceftazidime showed similar outcomes in both groups

Mode of antibiotic administration

• Intraperitoneal administration of abx is preferred over IV– Infection is usually localized to the peritoneum– Bacteremia is exceedingly rare (<1%)– Outpatient basis

• IP antibiotics can be given either– Continuous: abx given with each exchange– Intermittent: abx given once daily with a dwell of at

least 6 hours– No sufficient data to suggest that one is better than

other; usually equivalent

Staph. aureus peritonitis

Staph. Aureus on culture

D/c gram –ve coverage, cont. gram +ve coverage for 3 weeks

If MRSA change to Vancomycin and rifampin can be added (600 mg/day for 1 week)

If clinical improvement continue for 3 weeks

If no clinical improvement reculture and revaluate for exit-site or tunnel

Infection or intra-abd abscess

If peritonitis with exit-site or tunnel Infection – remove catheter

Allow 2 weeks rest period before reinitiating PD

If no improvement in 5 days on appropriate antibiotics, remove catheter

Enterococcus/Streptococcus peritonitis

Enterococcus/Strep on culture

D/c empiric coverageStart continuous Ampicillin 125 mg/L each bag

Consider adding aminoglycoside for enterococcus

If ampicillin resistant, start vanco;If VRE consider quinupristin/dalfopristin or linezolid

Clinical improvement; treat for 2 weeks – strep

3 weeks - enterococcus

No improvement, reculture and evaluate for exit-site or tunnel infection

Peritonitis with exit or tunnel infectionConsider catheter removal

Treat for 3 weeksIn no improvement by 5 days, remove catheter

Pseudomonas peritonitis

Pseudomonas on culture

W/o exit-site/tunnel infection With exit-site/tunnel infection

Remove catheterUse 2 abx with different mechanism

Oral quinolone, cephalosporin, piperacillinbased on sensitivities

If clinical improvementTreat for 3 weeks

If no improvement reculture andevaluate

If no improvement by 5 days on appropriate abx, remove catheter

Gram negative organism peritonitis

Single gram –ve organism on culture

E. coli, klebsiella or proteus

Stenotrophomonas

3rd generation cephalosporin:ceftazidime or cefepime

Two drugs with different mechanismsbased on sensitivity pattern

Duration of therapy: 3 weeks Duration of therapy: 3-4 weeks

If no clinical improvement by 5 days,remove catheter

Polymicrobial peritonitis

Polymicrobial peritonitis

Multiple gram –veorganisms

Multiple gram +veorganisms

Change to metronidazoleIn conjunction with ampicillin,

Ceftazidime or aminoglycoside

Surgical evaluation

Laprotomy for suspected intra-abdpathology/abscess with catheter removal

Continue therapy basedon sensitivities

W/o catheter infection,treat for 3 weeks

With catheter infection,remove catheter

Culture negative peritonitisCulture negative peritonitis

24-48 hours

Continue initial therapy

If culture negative for 72 hoursRepeat cell count and diff

Infection resolving, pt improving Infection not resolving

Cont initial therapy for 2 weeks,But D/c aminoglycoside if used initially

Special culture techniques forMycobacteria or legionella

Culture positive Culture negative

Adjust therapy as per sensitivity patternsIf no improvement in 5 days,Consider catheter removal

Other causes of peritonitis

• Fungal peritonitis– Catheter removal– Flucytosine 1gm/day + Fluconazole 200

mg/day PO for 10 days after catheter removal

• Mycobacterial peritonitis– M. tuberculosis: Rifampin + INH (for 12

months) + pyrazinamide + ofloxacin (3 months)

– Consider catheter removal

Antibiotic dosing recommendations for CAPD

Antibiotic Intermittent Continuous

Gentamicin 0.6 mg/kg LD 8, MD 4

Amikacin 2 mg/kg LD 25, MD 12

Cefazolin 15 mg/kg LD 500, MD 125

Cefepime 1 gm LD 500, MD 125

Cephalothin 15 mg/kg LD 500, MD 125

Ceftazidime 1 – 1.5 gm LD 500, MD 125

Ciprofloxacin No data LD 50, MD 25

Vancomycin 15-30 mg/kg every 5-7 days

LD 1000, MD 25

Aztreonam No data LD 1000, MD 250

Amphotericin NA 1.5

Imipenem/cilistatin 1 gm bid LD 500, MD 200

LD: loading dose in mg, MD: maintenance dose in mg

Intermittent dosing of antibiotics in APD

• Cefazolin (IP): 20 mg/kg every day, in long dwell

• Cefepime (IP): 1 gm in one exchange per day

• Vancomycin (IP): loading dose 30 mg/kg in long dwell, repeat dosing 15 mg/kg in long dwell every 5-7 days

• Fluconazole (IP): 200 mg in one exchange per day every 24-48 hours

Catheter removal in peritonitis patients

• 2005 ISPD guidelines recommend catheter removal in following– Relapsing peritonitis: another episode with same species that

caused the preceding episode within 4 weeks of completing abx– Refractory peritonitis: failure to respond to abx in 5 days– Refractory catheter infection– Fungal peritonitis– Fecal peritonitis– Peritonitis associated with intra-abdominal pathology

• Consideration to catheter removal in mycobacterial and multiple enteric organisms peritonitis

Other causes of cloudy effluent

• Eosinophilic peritonitis

• Chyloperitoneum• Fluid that’s been

dwelling for a long time

Eosinophilic peritonitis

• Relatively new PD catheter

• Effluent is cloudy w/o abdominal pain

• PD differential count: eosinophils ++

• Effluent culture: no growth

• Cause: ?immune reaction to catheter

• Treatment– Usually self limited, goes away in few days– Some reports of benefit with IP steroids

PD catheter removal after transplant

• Optimal time after transplant is unclear

• Some clinicians wait 3 – 4 months after transplant for catheter removal

• Early catheter removal is advised in high-risk patients

Case

• PD patient presents with abdominal pain– Diagnosed as peritonitis– PD effluent is clear– Pain localized to one spot– High peritoneal fluid amylase level on further

w/up

Other causes of abdominal pain in PD patients

• Ischemic bowel• Pancreatitis• Cholecystitis• Pyelonephritis• Nephrolithiasis• Constipation• Incarcerated hernia• Appendicitis• Diverticulitis• Ruptured viscous

Exit-site/Tunnel infection

• Exit-site infection: presence of purulent discharge with or w/o erythema of the skin at catheter-epidermal interface

• Tunnel infection: usually occult but may be present with erythema, edema or tenderness over subcutaneous path

• Rarely occurs alone• Staph aureus and pseudomonas exit site

infections are often associated with concomitant tunnel infection

Treatment of exit-site/tunnel infection

Purulent discharge from exit-siteDo culture/gram stain

Gram +ve organism Gram –ve organism

1st generationCephalosporin PO

PO Quinolones

If slow improvement or severeCases add Rifampin 600mg/day

If Pseudomonas and no improvement add 2nd

anti-pseudomonal; ceftazidime IP

Infection resolving; cont treatment for 2 weeks

Infection resolving; cont treatment for 2 weeks

Infection unresolved in 3-4 weeks;consider catheter revision/removal

Infection unresolved in 3-4 weeks;consider catheter revision/removal

Non-infectious complications

Non-infectious complications

Non infectious complications

Catheter related Catheter unrelated

•Outflow failure•Pericatheter leak•Abdominal wall herniation•Catheter cuff extrusion•Intestinal perforation

GERD HemoperitoneumBack/abdominal pain UF failureAbdominal wall herniation Peritoneal sclerosisPleural effusion Metabolic

Case

• A patient reports difficulty filling and draining– There is a positional component

– Catheter was placed several weeks ago. The dwell & drain has never been normal

– Bowel movements are normal and soft

– No fibrin noted in previous drains

Outflow failure

• Incomplete recovery of instilled dialysate– Unable to remove dialysate from peritoneal cavity– Fluid is no longer in peritoneal cavity

• Incidence: 5-20%• Etiologies

– Constipation (anytime)– Catheter malposition (days)– Intraluminal catheter occlusion by thrombus– Extraluminal catheter occlusion by omentum or

adhesions (weeks)– Kinking (soon after placement, positional)– Loss of dialysate from peritoneal cavity

Diagnosis

• History– Flow disturbance – inflow, outflow or both– When was the catheter placed– Constipation– Pain– Dyspnea– Fibrin in dialysate drain

• Plain film– Severe constipation– Catheter malposition

• Lost dialysate: peri-catheter dialysate leakage; either internal or external

Treatment

• Constipation– More than half of the cases are cured with releif of

constipation– Laxatives, stool softeners, suppositories or enema

• Fibrin clot– Heparin 500 units/L of dialysate for lysis– Urokinase – instilled in catheter for 1 hour and then

removed– Recombinant tPA – used if obstruction is refractory

Treatment

• Malpositioned catheter– Fluoroscopy with stiff wire manipulation– Redirection either laproscopically or surgically– Replace catheter if not successful

• Catheter kinking– Usually requires catheter replacement– Superficial cuff removal if kinking is due to placement

of the catheter cuffs too close to each other

• Abdominal exploration may be necessary for catheter redirection, omentectomy or adhesiolysis or catheter replacement

Case

• A 63 year old female started on CAPD 4 weeks ago is noted to have swelling of abdominal wall on regular visit. On history reports increased activity this week

Pericatheter leakage

• Early after placement• Increased intra-abdominal pressure on CAPD

2ry to increased activity• Weak abdominal wall (pervious surgeries,

pregnancies)• High dialysate volumes• Catheter placement techniques: poor evidence

of technique with incidence– Peritoneoscopically placed catheters may be better– Double cuff catheters are considered less likely to

leak

Pericatheter leakage

• Clinical features– Subcutaneous swelling– Fluid in area surrounding the catheter– Genital and abdominal wall edema– Diminished outflow volumes

• Diagnosis– Check glucose concentration of fluid around the

catheter to determine if it is dialysate or serous fluid from subcutaneous tissue

– For confirmation – peritoneal scintigraphy, CT scan or MRI after dialysate infusion using dialysate as a contrast

Pericatheter leakage

• Treatment– Reduce physical activity– Reduce dialysate volumes– Conversion to cycler– Temporary conversion to HD– If conservative measures fails then surgical

repair of deep cuff or catheter replacement

Case

• 42 year old female with h/o ADPKD started on CAPD 1 month back

• c/o progressive shortness of breath on exertion

• PD flow sheet reveals consistently inadequate UF

• On exam: normal BP, no edema, decreased breath sounds over right lung base

Pleural effusion

• Possible etiologies:– Volume overload, CHF– Local pleural process– Peritoneal dialysate

• Suspicion of peritoneal dialysate in a non edematous pt with inadequate UF

• Incidence: 1.6%, more common in females• ADPKD patients prone to have due to

decreased abdominal capacity

Pleural effusion

• Usually occurs early after starting PD• Unrelated to dialysate volumes• Hypotheses:

– Congenital communication between pleura and peritoneum. Dissection of fluid through defects around major vessels and the esophagus

– Combination of increased intra-abdominal pressure and negative intra-thoracic pressure may open small defects in the diaphragm

Pleural effusion

• Clinical features– Can be asymptomatic– Dyspnea on exertion– Inadequate UF– More common on right side – Occurs early after PD initiation, 50% of cases

within 1st month

• Diagnosis: high glucose concentration in pleural fluid

Pleural effusion

• Treatment: depends on acuity and severity– Thoracentesis – Drain peritoneal cavity and avoid overnight

supine dwells– If recurrent and unresponsive: chemical

pleurodesis using talc, tetracycline or autologous blood

– Surgical correction if diaphragmatic defect is identified

– Temporary conversion to HD

Catheter cuff extrusion

• Catheter cuff erodes through the skin to the outer abdominal wall

• Can be 2ry to exit-site infection or superficial cuff placement

• Incidence: 3.5 – 7%; no specific association with catheter type and method of placement

• Treatment: depends on presence or absence of infection– No infection: extruding cuff removed by opening the

subcutaneous tissue at exit site and trimming the cuff under sterile conditions

– Infection present: remove the catheter

Intestinal perforation

• Direct injury during catheter placement• By erosion – weeks to months after catheter placement• Requires high index of suspicion• Incidence: rare (<1%); more common with semi-rigid PD

catheters• Clinical features

– Bloody or feculent dialysate– Dialysate retention– Diarrhea after dialysate instillation– Gram negative peritonitis

• Treatment: surgery– Bowel repair, catheter removal and antibiotics

Bleeding exit-site

• Etiology– Trauma to small blood vessels after catheter

placement– Crust removal before natural separation

occurs– Exit-site infection with secondary hemorrhage

• If possible avoid peri-op anticoagulation for 24 hours

Case

• A 30 year old female reports pink tinged effluent

Hemoperitoneum

• Benign causes– Menstruation– Ovulation– Trauma– Coagulopathy– Ruptured renal or

ovarian cyst

• Serious causes– Ischemic bowel– Colon cancer– Pancreatitis– Encapsulating

peritoneal sclerosis– Urologic malignancy

During training, warn females in advance!

Hemoperitoneum

• Treatment– IP heparin to avoid clotting of catheter– Flushes– Investigations depend on suspected cause

and type of presentation

Case

• 45 year old female PD patient reports of epigastric discomfort

• No relation to food or exertion

• Usually occurs during a dwell period

GERD and delayed gastric emptying

• GERD: Clinical features– nausea, vomiting, fullness or discomfort– 24 hours pH monitoring has shown abnormalities after

dialysate instillation in symptomatic patients

• Delayed gastric emptying: mechanical or neurogenic mechanism triggered by the presence of intra abdominal fluid

• Treatment:– GERD: minimize supine intraperitoneal fluid volume– Delayed gastric emptying: metoclopramide or

erythromycin, case report of IP ondansetron in a patient with refractory symptoms

Case

• A 55 year old male undergoing CAPD for 2 years c/o dull lower back pain. The onset has been gradual over the past 6 months. Pain is 3/10 intensity, non-radiating, aggravated during dwell periods and while standing. Denies fever, wt loss, neurologic symptoms or trauma

• On exam– Normotensive– Non-tender abdomen– Slight lardosis +– Poor abdominal muscle tone– Neurologic exam: non focal

Back pain

• Can be 2ry to increased mechanical stress on lumbar spine (lardotic position)

• May be associated with other musculoskeletal disease

• Treatment– Decrease dialysate fill volumes– If inadequate dialysis, may need to change to

cycler (APD). Pt may tolerate larger fill volumes while supine

Case

• 48 year old male is on APD for one year

• Reports a new lump in his left groin

• He had been gardening and felt a ‘pop’ and some tenderness in groin

Peritoneal Scintigram

Hernia

• Treatment– Surgical repair– No PD for 2 days after surgery, then back on cycler,

day dwell can be re-introduced in 2 months– No need for interim HD

• Perioperative management of peritoneal dialysis patients undergoing hernia surgery w/o the use of interim HD; Shah et al, Perit Dial Int 2006; 684-687

Dialysate infusion pain

• Causes– Peritonitis– Patient new to PD. Pain diminishes during dwell– Acidic ph of conventional lactate dialysate– Catheter position abutting bowel wall– Dialysate temperature– High dialysate glucose concentration

• Treatment– Slow infusion rate– Dialysate with higher ph eg bicarb or bicarb/lactate– Injection of local anesthetic into dialysate before infusion eg 1%

lidocaine; 50mg/exchange– Incompletely drain the fluid after a dwell period– Rarely catheter replacement or conversion to HD

Metabolic

• Hypokalemia– 10 – 35% of PD patients require K supplements– Hypokalemia can be due to increased cellular K

uptake secondary to insulin secretion after glucose load

– Liberalize dietary K intake• Hypermagnesemia

– More common in PD than HD– Results from high Mg in dialysate (0.75 mmol/L)– Consider other dialysate conc (with Mg 0.5 or 0.25

mmol/L)– Avoid Mg containing medications

Encapsulating peritoneal sclerosis

• Rare• Inflammatory phase: non-specific symptoms like

nausea, vomiting, weight loss, high CRP, hypoalbuminemia

• Sclerosing phase: recurrent bowel obstruction, abdominal pain or hemoperitoneum, progressive malnutrition

• Incidence: 0.5 – 2.8%• Mortality: 38 – 63%• Both incidence and mortality increase with

increased time on PD

EPS: Diagnosis

• Markers of inflammation– Elevated CRP– Anemia, resistant to ESA’s– Hypoalbuminemia

• Radiology: CT scan– Peritoneal thickening– Peritoneal calcification– Tethering and cocooning of bowel– Small or large bowel obstruction

EPS: Treatment

• Corticosteroids:– Probably more useful in inflammatory phase– Both pulse steroids or daily therapy have been used– Encapsulating peritoneal sclerosis in Japan: a prospective,

controlled, multicenter study: Kawanishi et al; Am J Kidney Dis, 2004; 729-737

– Reported 38.5% remission rate with corticosteroids

• Tamoxifen: case reports• Surgical treatment

– Surgical lysis of intestinal adhesions and stripping of fibrous cocoon

– Indications for surgery: recurrent bowel obstruction, failing nutritional status, failure to respond to medical therapy