The Modern Management of Adhesions

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The Modern Management of Adhesions

• Michael C Parker BSc MS FRCS FRCS(Ed)
• Darent Valley Hospital
• Dartford, Kent, UK
• SCAR Panel Member
• Hungary 24th April 2004

2
Adhesions after colorectal surgery
Do we need to prevent?

• Yes

Do we need to treat?
3
Paradox of surgery the method proposed to
treat adhesions is the one that induces adhesions

• Need for clinical cost-effective agents to
  reduce adhesion development

4
Formation of Adhesions
5
Protection against adhesions
Injury


Bleeding
inflammation


Fibrin
deposition
Adhesions
6
Adhesion reduction strategies

• Careful surgical technique
• Minimise Inflammatory response
• Augmentation of fibrinolysis
• Adhesion-reduction agents

7
Applying adjuvantssolutions/drugs

• NSAIDs
• Most widely studied clinical efficacy is
  questionable
• Corticosteroids
• Poor efficacy associated with immunosuppression
  and delayed wound healing
• Fibrinolytics
• Risk of impaired wound healing and/or bleeding

Risberg B. Eur J Surg Suppl. 1997
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Adhesion Reduction Agents The ideal agent
According to recent surveys of surgeons the four
key attributes are

• Efficacy
• Operation site
• Throughout the cavity
• Economical

• Safety
• Easy to use
• General surgery
• Gynaecological surgery
• Open
• Laparoscopic

ESHRE 2002 Survey, EACP 2002 Survey
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Adhesion Reduction Agents

• Key issues
• Toxicity
• Handling
• Limited efficacy
• Clinical outcomes
• Cost

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Adhesion Reduction Agents
Withdrawn from US market
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Most Widely Used Adhesion Prevention Adjuvants

• Crystalloid instillates
• Lactated Ringers
• Saline
• Hartmanns Solution
• Limitations
• Absorbed within 24 hours
• They dont prevent adhesions!

13
Interceed Barrier (Oxidized Cellulose, Gynecare)

• First FDA approved adhesion reduction adjuvant
• Most clinical studies (24)
• Widely applicable
• all intraperitoneal locations
• all surgical procedures
• Compatible with laparoscopy
• Limited use in colorectal surgery
• Limitations
• Blood oozing renders it ineffective
• Irrigants must be removed
• Technical application challenges!

14
Seprafilm Membrane (HACMC, Genzyme)

• Widely applicable
• covers all intraperitoneal locations
• all surgical procedures
• Used in general surgery
• Limitations
• Handling
• Residual irrigation fluid must be removed
• Cannot be used via laparoscopy
• Cannot use at site of anastomosis
• Cost!!
• need mean 4.4 sheets in colorectal surgery!!!

Beck et al Dis Colon Rectum 2003461310-1319
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SprayGel (Polyethylene Glycol Polymer, Confluent)

• Polymerization
• Methylene blue to show where it is used

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SprayGel (Polyethylene Glycol Polymer, Confluent)
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SprayGel
Laparoscopic Kit
Requires specialised air pump
Open Surgery Kit
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SprayGel
5 kits needed for complete peritoneal coverage!!!
Korell Adhesions News Views 2004 in press
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SprayGel

• Limitations
• complex set-up
• time consuming
• limited efficacy safety data
• US regulatory study halted
• cost

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SprayGel

• Limitations
• complex set-up
• time consuming
• limited efficacy safety data
• US regulatory study halted
• cost
• particularly 5 kits!

Korell Adhesions News Views 2004 in press
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SurgiWrap (polylactide copolymer film, Macropore)

• Peritoneal replacement film
• Suture in place
• Remains for 6 months
• Excreted through lungs
• Limitations
• Data limited safety and efficacy
• Handling??
• Cost!!

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Adept New solution to adhesion reduction?
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Adept - icodextrin 4 solution

• ? 1,4 linked glucose polymer
• Icodextrin 4 solution
• isosmolar
• biocompatible
• well-established safety profile at 7.5
  concentration
• gt36,000 patient years safety data from renal use
• 50,000 patients treated with Adept
• persists in peritoneal cavity
• reduces adhesion formation through physical
  action
• hydroflotation

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Adept hydroflotation mechanism
Hosie et al Drug Delivery 2001
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Adept use- Irrigation - minimum
100mls/30mins - Laparoscopy through the
scope - Laparotomy via a syringe
- Instillation - 1000ml at closure

• Laparoscopy

• Laparotomy

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Adept (Icodextrin 4, Shire Pharmaceuticals)

• Used as an irrigant and an instillate
• Covers all intraperitoneal locations
• Easy to use
• laparoscopic clinical studies
• laparotomy registry feedback
• Not constrained by oozing
• Residual irrigation solution is not a problem
• Extensive safety experience at 7.5
• ARIEL Registry of routine use in gt4,600 patients
• feedback of use and safety good
• Promising early results
• Modest cost
• Limitations
• Limited clinical data at present extensive
  work in progress

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Surgical procedures and adjuvant use
O not used/recommended
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Adhesion reduction agents status
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Cost comparison
SurgiWrap estimate 150 (225)/sheet
UK sterling prices equivalent
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Cost comparison
SurgiWrap estimate 150 (225)/sheet
UK sterling prices equivalent
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Prophylaxis?

• Adoption of routine prophylaxis
• depends on impact of strategy on
• adhesion-related readmissions
• and cost of strategy

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Cost-effectiveness

• Costs of adhesion-related Small Bowel Obstruction
• Conservatively treated 1,606 (mean stay 7 days)
• Surgically treated 4,677 (mean stay 16 days)
• Adhesion reduction technologies may reduce costs

Menzies, Parker et al. Ann Roy Coll Surg Engl.
2001
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Modelling cost effectiveness- lower abdominal
surgery
If adhesion-related readmissions are reduced by
the routine use of an adhesion reduction agent,
whats the cost impact?

• Assume agent costs 200
• Assume agent costs 50
• What efficacy is required to payback the cost of
  using an anti-adhesion agent at 3 years???

Wilson et al. Colorectal Dis. 2002
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Cumulative cost of adhesion-related readmissions
following lower abdominal surgery
Cumulative cost/100 patients
Wilson et al Colorectal Dis 2002
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Cumulative cost of adhesion-related readmissions
following lower abdominal surgery
70,000
Control
16
60,000
50
50,000
40,000
Cumulative cost/100 patients
30,000
20,000
10,000
0
1
2
3
4
5
6
7
8
9
0
Years since surgery
Wilson et al Colorectal Dis 2002
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Modelling cost effectiveness- lower abdominal
surgery
Routine use of an anti-adhesion agent costing 50
will payback the investment cost if it reduces
adhesion-related readmissions by only 16 after 3
years

• Agents costing 200 or more are unlikely to
  payback
• the costs of usage

Wilson et al. Colorectal Dis. 2002
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Modeled cumulative cost savings in the UK Lower
abdominal surgery (158,000 ops per year) SCAR
150
125
50 product (assume 25 efficacy)
Saving 71m
100
75
50
25
Cumulative cost savings (Millions)
0
-25
-50
-75
-100
-125
-150
1
2
3
4
5
6
7
8
9
Loss 142m
200 product (assume 25 efficacy)
Time since start of adhesion-reduction treatment
policy with product (years)
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Use of anti-adhesion agents

• vs High Risk Surgery
• Adhesiolysis
• Small bowel resection
• Formation of stoma
• Hartmanns procedure
• Anterior resection
• Abdomino-perineal excision
• Colectomy
• Surgical treatment of peritonitis fistulae

• Routine prophylaxis

Or do nothing???
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Implications of doing nothing

• Adhesions are inevitable
• High risk of adhesion-related problems
• Small bowel obstruction
• Female infertility
• Chronic and debilitating pelvic pain
• Reoperative complications
• Do we tell our patients when we obtain consent?

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Informed consent

• International Adhesions Society Patient Survey
• In only 10.4 of cases adhesions mentioned as
  part of informed consent process
• 14.4 adhesions discussed but not part of consent
• Adhesiolysis patients
• 54 given some information before surgery
• 46 given specific information about
  anti-adhesion agents
• In non-adhesiolysis procedures only 10 patients
  advised about adhesions
• Only 6 given information on anti-adhesion agents

Wiseman, Adhesions News Views 4 2003 and PAX
Meeting 2003
42
Medico-legal consequences

• Most common claims
• Failure to diagnose / delay in diagnosis
• Failure to take precautions to prevent
• Bowel damage at adhesiolysis
• Infertility / risk of infertility
• Chronic abdominal / pelvic pain
• Starch granuloma (gloves)
• 1995-1999 UK MDU received 77 adhesion-related
  claims
• Average settlements 50,765

Before SCAR Before we knew the real extent of
the problem Before we had newer anti-adhesion
agents
Ellis H, Journal of the Royal Society of Medicine
2001
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Where are we now?

• Adhesions continue to be a significant burden
• For the patient
• pain, SBO, infertility, re-operative
  complications
• For the surgeon
• increased workload, lengthy and complex
  procedures, medicolegal consequences
• For the healthcare system
• increased workloads, costs, bed stay

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Where are we now?

• Any advances in surgery have had little impact
• Action on adhesions has received low priority
• even in high risk procedures
• New developments in anti-adhesion agents
• not all are difficult or costly to use
• emerging evidence of efficacy

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Adopt use of anti-adhesion agents in High Risk
surgery

• Adhesiolysis
• Small bowel resection
• Formation of stoma
• Hartmanns procedure
• Anterior resection
• Abdomino-perineal excision
• Colectomy
• Surgical treatment of peritonitis fistulae

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Acknowledgments

• Fellow SCAR Panel Members
• Prof Harold Ellis, UMDS, London
• Malcolm Wilson, Christie Hospital, Manchester
• Don Menzies, Colchester Hospital, Colchester
• Jeremy Thompson, Chelsea Westminster Hospital,
  London
• Brendan Moran, North Hampshire Hospital,
  Hampshire
• Adrian Lower, St Bartholomew's Hospital, London
• Rob Hawthorn, Southern General Hospital, Glasgow
• Prof Alastair McGuire, City University, London
• Graham Sunderland, Southern General Hospital,
  Glasgow
• David Clark, James Boyd, Alan Finlayson, ISD, NHS
  Scotland, Edinburgh
• Prof Ian Ford, Robertson Centre Biostatistics,
  Glasgow
• Alastair Knight Alison Crowe, Corvus
• Shire Pharmaceuticals Group plc

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Thank you