01Principles and purposeThe professional or clinical skill and the decisions it supports.
Cholestatic itch is not a histamine-driven rash. Retained bile-associated pruritogens and altered neural signalling contribute, so antihistamines may sedate without addressing the mechanism. Ask about timing, palms and soles, sleep, scratch injury, mood and treatment interference. Bilirubin and itch severity correlate poorly. Mechanical obstruction should be mapped and relieved when appropriate before escalating symptom medicines.
Colestyramine binds bile acids in the gut and is a practical initial medicine when some bile reaches the intestine. Its powder must be suspended before swallowing, and its broad binding action reduces absorption of warfarin, levothyroxine, digoxin and many other drugs. Constipation and long-term fat-soluble vitamin deficiency limit use. Complete obstruction is a contraindication because no intestinal bile is available to bind.
Cholangitis combines bacterial infection with impaired drainage. Stones, malignant strictures, blocked stents and postoperative narrowing are common settings. Classical Charcot features may be incomplete, particularly in older or immunosuppressed adults. Sepsis care, cultures, renal-adjusted antibiotics and urgent source control proceed together. Once stable, supportive care includes nutrition, vitamin assessment, pain and nausea control, sleep, psychological support and a named route for recurrent obstruction.
Key points
- Cholestatic pruritus often worsens at night and may cause excoriation, insomnia, low mood and poor function; measure its severity and effect rather than relying on bilirubin level.
- Look for reversible obstruction first. Drainage may relieve itch in mechanical blockage, while colestyramine requires bile acids to reach the intestine and is ineffective in complete biliary obstruction.
- A licensed adult pruritus regimen is colestyramine 4 g orally once daily, increasing to 4 g twice daily if needed; mix each sachet with liquid and separate other medicines by at least one hour before or four to six hours after.
- Suspect cholangitis from systemic infection plus biliary obstruction even without the full fever-pain-jaundice triad; send blood cultures and examine existing stent anatomy.
- A current named NHS adult example is co-amoxiclav 1.2 g IV every 8 hours, reviewed at 48–72 hours and stepped down to 625 mg orally every 8 hours when improving, for 5–7 days total according to severity and progress.
- If the DBTH patient is older than 65 years and received co-amoxiclav or a cephalosporin in the preceding 2 weeks, that protocol uses piperacillin/tazobactam 4.5 g IV every 8 hours instead; allergy and renal impairment require specific alternatives or adjustment.
- For adult sepsis fluid resuscitation, NICE NG253 uses 250 mL isotonic crystalloid over 10–15 minutes, reassessing after each bolus and giving further 250 mL boluses only as needed up to 1,000 mL total.
- Antibiotics and fluids stabilise the patient but do not clear a blocked duct; arrange ERCP, percutaneous or expert EUS-guided drainage according to the obstruction.
02Situations and prioritiesThe context, relevant information and actions that matter most.
Pruritus without a primary rash, often nocturnal and involving palms or soles, accompanies bile-flow impairment but can occur at any bilirubin level.
Excoriation, bleeding, secondary infection and sleep loss show disease burden and provide outcomes against which to judge treatment.
Fever or rigors with jaundice, biliary pain, cholestatic tests or known stent dysfunction is sufficient to investigate and treat urgently.
Confusion, low blood pressure, low urine output, hypoxaemia or lactate rise marks severe sepsis and accelerates drainage and critical-care review.
Return of dark urine, pale stool, itch, fever or pain after previous decompression suggests recurrent mechanical failure rather than isolated symptom relapse.
03Assessment and interpretationHow to gather information, assess the situation and recognise uncertainty.
Consider the information, its meaning and its limitations before deciding what follows.
- 01
Sepsis observations, lactate and glucose - Why
- Identify hypoperfusion and immediate organ threat and guide repeated response assessment.
- Interpretation and limitations
- Normal initial blood pressure does not exclude evolving sepsis; trend mental state, urine output, capillary refill, respiratory status and lactate.
- 02
Blood cultures and full blood count - Why
- Document bacteraemia and inflammatory or marrow response before antibiotics when this does not delay treatment.
- Interpretation and limitations
- Negative cultures do not exclude duct infection, especially after antibiotics; bile culture at drainage can guide later narrowing.
- 03
Bilirubin, ALP, ALT, INR and renal profile - Why
- Measure obstruction, liver function, dehydration and dose-adjustment needs.
- Interpretation and limitations
- A bilirubin plateau after intervention suggests incomplete drainage, device failure or hepatic infiltration; rising creatinine changes antibiotic and contrast decisions.
- 04
Urgent ultrasound or cross-sectional imaging - Why
- Locate duct dilatation, stent position, mass, stone, abscess and undrained sectors.
- Interpretation and limitations
- Use available imaging without delaying source control in shock; hilar anatomy may require CT or MRCP interpretation to select the infected segment.
- 05
Pruritus baseline assessment - Why
- Measure itch intensity, sleep disruption, skin injury and patient-defined function before treatment.
- Interpretation and limitations
- Review the same outcomes after drainage or medicine; a bilirubin change without symptom improvement should not be labelled successful itch control.
- 06
Fat-soluble vitamins and nutrition review - Why
- Detect consequences of prolonged cholestasis, reduced intake and bile-acid sequestration.
- Interpretation and limitations
- Check weight trend and dietary intake; use coagulation and targeted vitamin testing according to duration, bleeding, bone risk and planned procedures.
04Worked approachesCases with ordered reasoning, an action and a check of the outcome.
01Worked case: stent cholangitis with verified source controlTreat infection and the obstructionA 76-year-old with a metal stent for distal cholangiocarcinoma has rigors, confusion, BP 84/52 mmHg, lactate 3.8 mmol/L, bilirubin 164 micromol/L and new duct dilatation above the stent. CrCl is 38 mL/min, co-amoxiclav was taken eight days ago, and there is no beta-lactam allergy or previous co-amoxiclav-associated hepatic injury.+
- 1Recognise high-risk stent-cholangitis sepsis and take blood cultures without delaying antibiotics beyond one hour. Age over 65 plus co-amoxiclav in the preceding two weeks selects the DBTH piperacillin/tazobactam branch: give 4.5 g IV every eight hours over 30 minutes, within the selected product maximum for CrCl 20–40 mL/min, while arranging urgent drainage.
- 2Give 250 mL balanced isotonic crystalloid over 10–15 minutes; after each bolus reassess pressure, lungs, capillary refill and urine output, stopping at 750 mL when perfusion improves rather than automatically infusing a fixed large volume.
- 3Urgent ERCP demonstrates tumour ingrowth and pus above the occluded stent; the endoscopist clears debris and places a new internal stent that restores bile flow.
- 4After ERCP, lactate falls to 1.6 mmol/L within 24 hours and mentation/urine output normalise. Blood and bile grow co-amoxiclav-susceptible E. coli. At 72 hours the patient is afebrile, absorbs tablets and CrCl has recovered to 55 mL/min; the infection team stops piperacillin/tazobactam and selects co-amoxiclav 500/125 mg orally every eight hours with food to complete seven days total. Falling bilirubin and sustained recovery support stopping at that review point; recurrent fever triggers renewed drainage assessment.
02Obstructive pruritusRelieve the cause before escalating tabletsA patient with progressive jaundice and disabling itch has imaging evidence of a drainable distal malignant obstruction.+
- 1Document itch and sleep severity, examine excoriations and review medicines and coagulation.
- 2Agree definitive or palliative decompression through the HPB team rather than relying on antihistamine sedation.
- 3After successful drainage, reassess itch and bilirubin; use colestyramine only if symptoms persist and bile is entering the intestine.
- 4Separate interacting medicines and stop or escalate therapy based on measured benefit, constipation and nutritional effects.
03Refractory itchEscalate through specialist monitoringPruritus continues despite patent drainage and a tolerated, correctly separated colestyramine trial.+
- 1Reconfirm stent patency and exclude primary dermatological disease, uraemia, iron deficiency and medicine-related itch.
- 2Refer to hepatology or palliative care for a monitored second-line strategy such as rifampicin, opioid antagonism or serotonergic treatment selected for comorbidity.
- 3Define baseline liver tests, interactions and the stopping rule before the new medicine begins.
- 4Review itch, sleep, toxicity and laboratory response promptly and discontinue an ineffective or harmful treatment.
05Relevant medicines and safetySpecific regimens and precautions when the skill involves prescribing.
Colestyramine 4 g sachets for cholestatic pruritus
Start one 4 g sachet by mouth once daily; if needed and tolerated, use one 4 g sachet twice daily, because the current SmPC states that one or two sachets daily are usually sufficient for pruritus. Mix each dose thoroughly with water or another suitable liquid and never swallow the dry powder. Give other oral medicines at least 1 hour before or 4–6 hours after colestyramine.Do not use in complete biliary obstruction because it cannot work without bile entering the gut. Constipation is common and may require dose reduction; prolonged high-dose use can reduce absorption of vitamins A, D and K and cause bleeding tendency. Review warfarin, levothyroxine, digoxin, diuretics, anticonvulsants and other interacting oral medicines. The cited product contains sucrose, relevant to diabetes and rare sugar disorders. Prolonged high doses can cause hyperchloraemic acidosis, particularly with renal impairment; spironolactone increases this risk. Safety in pregnancy and breastfeeding is not established, and interference with fat-soluble vitamin absorption requires specialist benefit-risk and nutritional assessment.
Co-amoxiclav for acute cholangitis: current DBTH adult example
The named DBTH September 2025 adult cholangitis regimen is co-amoxiclav 1.2 g IV every eight hours, given by slow injection over 3–4 minutes or infusion over 30–40 minutes. Give high-risk sepsis antibiotics within one hour. Review at 48–72 hours after drainage; if improving and absorbing tablets, switch to 500/125 mg orally every eight hours with food for 5–7 days total according to severity/response. If age is over 65 AND co-amoxiclav or a cephalosporin was taken in the preceding two weeks, use piperacillin/tazobactam 4.5 g IV every eight hours over 30 minutes instead, with culture-directed de-escalation.Exclude penicillin/component hypersensitivity, severe immediate hypersensitivity to another beta-lactam and previous co-amoxiclav-associated jaundice/hepatic dysfunction. For IV co-amoxiclav at CrCl 10–30 mL/min, give initial 1,000/200 mg then 500/100 mg every 12 hours; below 10, give the same initial dose then 500/100 mg every 24 hours. For oral 500/125 mg, CrCl 10–30 uses one tablet every 12 hours and below 10 every 24 hours; dialysis has separate instructions. Piperacillin/tazobactam maximum frequency is 4.5 g every eight hours at CrCl 20–40 and every twelve hours below 20; infuse over 30 minutes. Reassess renal function, electrolytes, blood count, liver tests and allergy suitability, review interacting medicines and use the receiving unit’s allergy/microbiology pathway when this example is unsuitable.
06Feedback, follow-up and evidenceReview outcomes, seek feedback and identify what to improve.
- During acute cholangitis, reassess observations, capillary refill, mental state, oxygen need, urine output and lactate after each intervention and escalate persistent shock to critical care.
- Review antimicrobial choice at 48–72 hours with blood and bile cultures, renal function, source-control success and a documented total stop date.
- After decompression, trend fever, bilirubin, ALP and inflammatory markers and investigate a plateau or relapse for an undrained sector or failed stent.
- For itch, repeat the same sleep and severity measure after each change; monitor constipation, adherence, timing around other medicines and fat-soluble vitamin risk.
- Give patients and carers a direct contact number and exact return symptoms for stent blockage, sepsis, bleeding, dehydration and treatment toxicity.
- Include dietitian, HPB nurse and palliative-care support early when weight loss, fatigue, mood, pain or complex home drain care limits quality of life.
07Special situationsVariants, exceptions and circumstances that change the usual approach.
Itch is not bilirubin
Symptom severity may be profound with modest biochemical change, so treatment response must include sleep, skin and function.
Colestyramine needs intestinal bile
The medicine cannot bind a substrate that never reaches the bowel, making complete obstruction a mechanistic contraindication.
Antibiotics buy source-control time
Clinical improvement after the first dose does not remove an occluded stent or decompress an infected isolated sector.
Small boluses need reassessment
NICE's 250 mL sepsis bolus is followed by physiological review, allowing resuscitation to stop before pulmonary overload.
Support is active treatment
Nutrition, sleep, skin care, psychological help and a reliable contact pathway determine whether complex biliary care remains tolerable.
08Common pitfallsFrequent interpretation and management errors.
- 01
Prescribing an antihistamine alone for cholestatic itch may add sedation while leaving obstruction and bile-acid mechanisms unaddressed.
- 02
Giving colestyramine at the same time as warfarin or levothyroxine can reduce absorption and destabilise another important condition.
- 03
Waiting for the complete Charcot triad before treating cholangitis misses older or immunosuppressed patients with incomplete presentations.
- 04
Continuing broad-spectrum antibiotics without drainage or a stop review fails both source control and antimicrobial stewardship.
- 05
Giving a large unassessed crystalloid volume ignores the current NICE sequence of 250 mL boluses with review after each.