Outcome of transplant surgery performed outside

the regular working hours

Jore Hendrikx

Prof. Dr. S. Rex

Overzicht

• Achtergrondinformatie

• Hypothese

• Methode en materialen

• Resultaten

• Conclusie

Background information• 2000: rapport van the American National Academy of Medicine:

- 98 000 doden jaarlijks < medische fouten

- Chirurgische complicaties: 2e meest voorkomende oorzaak(Kohn, et al: To Err is Human: Building a Safer Health System. National Academy Press)

• Sindsdien veel onderzoek naar de verbanden tussen slaapdeprivatie en medische fouten

• Voor heelkunde specifiek: geen eenduidig verband tussen slaapdeprivatie en slechtere

outcome in morbiditeit en mortaliteit

• Toegenomen mortaliteit bij niet electieve operaties uitgevoerd ‘s nachts(Pearse, et al: Mortality after surgery in Europe: a 7 day cohort study. The Lancet 2012; 380: 1059-65)

Background information

• Transplantaties: specifieke heelkunde

1. Ernstige onderliggende pathologie

-> reeds hoger perioperatief risico

2. Non-electieve procedures

-> onvoorspelbare start heelkunde

• Risico bij uitstel van transplantaties

– Kwaliteit van donororgaan in gedrang door toegenomen risico op cardiocirculatoire

instabilisatie van donor

– Interferentie met electieve operatie-programma

– Reservatie van ICU bedden en dus andere opnames blokkeren

– Negeren van wens van familie

– Toegenomen ischemie tijden als recipient heelkunde wordt uitgesteld

Hypothesis

Is er een verband tussen startuur van

transplantatie-chirurgie en outcome van de

patiënt?

Methods & materials: datasearch

• PubMed database

• Search strategy: zoektermen gebaseerd op 3 concepten

1. Transplant surgery

2. Time factors

3. Outcome

• Review referenties van relevante artikels

Methods & materials: study selection

• Inclusie criteriaVergelijking van outcome voor transplant-chirurgie tussen dag/nacht of

weekend/week

• Exclusie criteriaCase reports, comments, discussion letters, no full text available, conference

abstracts, alle talen in niet-Engels, pediatrische populatie

• Primary outcomeMortaliteit na bepaalde duur (7 dagen, 30 dagen, 1 jaar, ..)

• Secondary outcomeComplicaties gerelateerd aan heelkunde

Results

• PubMed search: 11 796 citaten

• 11 relevante artikels: retrospectieve cohort studies– 8 niertransplanten

– 2 levertransplanten

– 1 thoracale orgaan transplanten

Results: Renal transplant surgery

Renal transplants

Author, country,

date

Patient group Donor type Outcomes measurements Results (%) Results reference P value Adjusted HR (95%

CI)

Comments

Anderson et al,

England 2016

January 2003 – December 2014

(N = 12 902)

Weekday: Monday to Thursday

(N = 7724, 60%)

Weekend: Friday to Sunday

(N = 5178, 40%)

DCD: 25.8% (week)

vs 24.2% (weekend)

DBD: 20.9% (week)

vs 21.3% (weekend)

Mortality

30 days

1 year

Allograft complications

Kidney allograft failure/rejection <1 year

DGF

Health resource implications

LOS (days)

1-year readmission risk

0.9

3.7

16.7

29.97

10 (7-15)

63.3

1.2

3.8

16.8

29.36

10 (7-14)

63.5

0.13

0.79

0.90

0.46

0.001

0.77

1.01(0.84-1.21)

1.00(0.91-1.09)

0.99(0.92-1.07)

No inferior short-term outcome on 1-year risk for

rehospitalisation, mortality and failure/rejection for renal

transplants performed on weekdays. Length of stay was

significantly longer for weekday surgery.

Baid-Agrawal et al,

USA 2016

April 1994 – September 2010

(N =136 715)

Weekday: Monday to Friday

(N = 99 061, 72%)

Weekend: Saturday or Sunday

(N = 37 654, 28%)

DCD Primary outcomes

Patient survival

Death-censored survival

Overall allograft survival

Secondary outcomes

Dialysis within the first week

LOS

Acute rejection in the first year

24.6

6 (5-10)

12.7

24.9

7 (5-9)

12.7

0.43

0.49

0.29

0.70

0.001

0.07

1.01(0.92-1.04)

1.01(0.99-1.03)

1.01(0.98-1.04)

The day of surgery does not affect the outcome of renal

transplants. A shorter length of stay was the only

significant association (6 days vs. 7 days) with transplants

performed during the weekend.

Manfredini et al,

Italy 2016

January 2000 – December 2013

(N = 9063)

Weekday: Monday to Friday

(N = 7572, 84%)

Weekend: Friday 12 pm to Sunday 12 pm

(N = 1491, 16%)

Unknown LOS (days)

In-hospital mortality

Cardiovascular events

10.5 (±10.8)

21.0

4.0

9.5 (±12.3)

19.8

4.0

0.001

ns

ns

Renal transplant recipients are not exposed to higher risk of

adverse outcome during weekend transplantations. Only

duration of hospitalisation was increased.

Özdemir- van

Brunschot et al,

The Netherlands

2015

January 2000 – December 2013

(N = 4519)

Day: 8 am – 8 pm (N = 3039, 67%)

Night: 8 pm – 8 am (N = 1480, 33%)

DCD: 42.1% (day) vs

36.4% (night)

DBD: 57.9% (day) vs

63.2 (night)

Primary outcome

Technical graft failure excluding PNF and NVK

Secondary outcome

Technical graft failure including PNF and NVK

Acute rejection within 10 days

1.0

3.3

0.3

2.6

4.4

0.2

0.00

0.08

0.51

Daytime surgery was an independent predictor of pure

technical graft failure.

Fechner et al, USA

2008

1994 – 2004

(N = 260)

Day: 8 am – 8 pm

(N = 166, 64%)

Night: 8 pm – 8 am

(N = 94, 36%)

Unknown Graft failure

1 year

5 years

All complications, required re-operation <30d

Ureteral

Vascular

Thrombosis graft vein

Hematoma

Nephrectomy for ischemia

10.6

20.2

16.8

2.1

8.5

1

4.2

1

6.6

8.4

6.4

1.6

1.6

0

1.6

1.6

< 0.05

< 0.01

ns

< 0.01

ns

ns

ns

Surgery performed at night enhances the risk for

complication and graft failure.

Kienzl-Wagner et

al, Austria 2013

January 2000 – December 2009

(N = 873)

Day: 8 am – 8 pm

(N = 610, 70%)

Night: 8 pm – 8 am

(N = 263, 30%)

Deceased donors, not

futher specified

Primary endpoints

Patient survival

1 year

5 years

Graft survival

1 year

5 years

Secondary endpoints

Delayed graft function

Acute rejection

Surgical complications

94.6

86.3

90.4

78.1

37.6

18.3

22.4

95.9

88.0

90.3

78.3

31.1

22.6

22.1

0.73

0.78

0.06

0.15

0.92

Night-time kidney transplants are neither associated with

poorer graft or patient survival nor higher surgical

complication rates.

Seow et al, UK

2004

January 1998 – June 2001 (N = 322)

Day: 7.30 am – 6 pm (N = 138, 43%)

Evening: 6 – 12 pm (N = 139, 43%)

Night: 00 – 7.30 am (N = 45, 14%)

Deceased donors, not

further specified

Complications overall Evening: 26.1

Night: 30.2

20 Complication rates are not increased when operating out of

hours. Moreover a prolonged CIT had no effect on

incidence of complications.

Additional research did detect a decrease in complication

ratio when a surgical consultant was present.

Shaw et al, USA

2012

March 2000 – December 2008

(N = 633)

Day: 6 am – 6 pm

(N = 415, 66%)

Night: 6 pm – 6 am

(N = 208, 34%)

DCD: 16.3% (day) vs

14.5% (night)

DBD: data not given

Primary outcomes

LOS (days)

ICU LOS (days)

DGF

Complications

Wound related

Vascular

Urological

Gastro-intestinal

Bleeding

10

2.0

31.7

12.0

8.2

1.4

2.4

1.9

0.5

9.3

2.3

34.5

11.3

7.2

3.6

1.2

0.7

0.7

0.2

0.2

1.0

0.8

0.6

0.04

0.2

0.2

0.8

0.99 (0.66-1.49)

1.07 (0.59-1.92)

1.19 (0.59-2.40)

0.12 (0.01-0.94)

2.69 (0.57-12.74)

3.38 (0.54-21.25)

0.71 (0.07-7.22)

Only vascular complications were slightly less frequent to

occur during night-time surgery.

• 8 studies: in totaal164 965 patiënten

Week vs weekend: 158 680 patiënten, dag vs nacht: 6285 patiënten

• Geen verschil in outcome: 2 studies

• Slechtere outcome bij transplantaties na de kantooruren

– Toegenomen hospitalisatie duur in 2 studie (weekend groep)

– Toegenomen risico op complicaties en orgaan falen (nachtgroep)

• Betere outcome bij transplantaties uitgevoerd na de kantooruren

– Verminderde hospitalisatie duur in 1 studie (weekend groep)

– Verminderd technisch orgaan falen 1 studie (nacht groep)

– Minder vasculaire complicaties in 1 studie (nacht groep)

Results: Renal transplant surgery

Results: Liver transplant surgeryAuthor, country,

date

Patient group Donor type Outcomes measurements Results (%) Results

reference

P value Adjusted HR (95% CI) * Comments

Orman et al,

USA 2012

October 1987 – December 2010

(N = 94 768)

Day: 7 am – 7 pm

(N = 51 543, 62%)

Night: 7 am – 7 am

(N = 31 143, 38% )

Weekday: Monday 8 am – Friday

5 pm

(N = 59 580, 65%)

Weekend: Friday 5 pm – Monday

8 am

(N = 32 079, 35%)

82% of all

donors were

deceased of

whom 3% DCD

Mortality

30 days

90 days

365 days

Graft failure

30 days

90 days

365 days

Mortality

30 days

90 days

365 days

Graft failure

30 days

90 days

365 days

Night

4

7

14

7

11

19

Weekend

5

8

14

8

12

20

Day

4

8

14

8

12

19

Weekday

5

8

14

8

12

19

0.89

0.39

0.26

0.21

0.94 (0.85-1.05)

0.98 (0.90-1.06)

0.99 (0.94-1.05)

1.00 (0.92-1.08)

1.00 (0.94-1.06)

1.01 (0.96-1.06)

0.93 (0.84-1.04)

0.98 (0.91-1.06)

1.02 (0.97-1.08)

1.04 (0.96-1.13)

1.04 (0.97-1.10)

1.05(1.01-1.11)

Night-time and weekend operations for

liver transplantations did not affect graft

or patient survival. There is a statistically

significant decline in graft survival 365

days after transplantation when the

surgery occurred during the weekend

Lonze et al, USA

2010

June 1995 – October 2008

N = 578

Day: 3 am – 3pm

(N = 388, 67%)

Night: 3 pm – 3 am

(N = 190, 33%)

6.1% of all

donors were

DCD.

Postoperative complications

Wound related

Vascular

Biliary

Other

Early deaths < 1 week

Sepsis

PNF

Operative time (h)

PRBC (units)

FFP (units)

5 –year survival

40.4

13.7

14.2

16.3

9.5

6.3

7.9

1.6

9.6

9.8

11.7

34.3

12.1

9.5

16.2

10.6

2.8

5.4

2.8

9.1

8.2

10.4

0.1

0.4

0.1

0.9

0.6

0.02

0.3

0.6

0.03

0.1

0.2

0.5

1.34 (0.93-1.94)

1.24 (0.72-2.15)

1.56 (0.90-2.68)

1.03 (0.64-1.67)

0.84 (0.46-1.54)

2.85 (1.16-7.00)

1.55 (0.74-3.25)

1.50 (0.33-6.86)

42.19(4.98-79.39)

1.14 (0.96-1.35)

Complications were not significantly

different but night-time transplants were

longer in duration and associated a

twofold greater risk of early death

compared to daytime transplant.

Long-term survival did not differ between

the subgroups.

HR = hazard ratio; CI = confidence interval; DCD = donation after cardiac death; PNF: primary graft non-function; PRBC: packed red blood cells; FFP: fresh frozen plasma

* Lonze et al. adjusted HR for recipients age, race, gender, body mass index (BMI), model for end-stage liver disease (MELD) score, indication for transplantation, diabetes, transplantation as Status 1, donor age, gender,

body mass index, donation after cardiac death (DCD), and CIT.

Orman et al. adjusted HR for nighttime procurement, CIT, donor age, graft type (split liver), DCD, recipient sex and age, indication for transplantation, donor location, dialysis, vasopressor use, portal vein thrombosis,

previous abdominal surgery, retransplantation, and pre-MELD era versus MELD era

Results: Liver transplant surgery• 2 studies: in totaal 95 346 patiënten

• 1 studie: zowel nacht vs dag als weekend vs weekdag

• Geen verschil in outcome:

– De studie van Orman die dag en nacht transplantaties vergelijkt,

• Slechtere outcome bij transplantaties na de kantooruren

– Verminderde overleving na 365 dagen (weekend groep)

– Toegenomen operatie duur en verdubbeld risico op vroegtijdige dood (nacht

groep) MAAR geen verschil in lange termijn overleving tussen beide groepen,

Results: Thoracic organ transplant surgeryAuthor, country,

date

Patient group Donor

type

Outcomes measurements Results (%) Results reference P value Adjusted HR (95% CI) * Comments

George et al,

USA 2016

January 2000- June 2010

(N = 27 118)

Day: 7 am - 7 pm

(N = 8 346, 70% )

Night: 7 pm - 7 am

(N = 8 227, 30%)

Unknown Heart transplantsSurvival

30 days

90 days

365 days

Complications

Reoperation need

Pacemaker placement

Noncardiac surgery

Infection

Cerebrovascular accident

New-onset dialysis

LOS (days)

Lung transplantsSurvival

30 days

90 days

365 days

Complications

Reoperation need

Pacemaker placement

Noncardiac surgery

Infection

Cerebrovascular accident

New-onset dialysis

LOS (days)

Night

95.2

92.7

87.7

11.99

3.85

16.08

23.89

2.17

9.01

14 (10-21)

Night

95.5

91.7

82.6

2.08

0.23

19.22

43.15

1.98

5.79

15 (10-26)

Day

95.0

92.6

88.0

11.54

3.38

15.25

24.34

2.43

8.51

14 (10-20)

Day

96.0

92.7

83.8

2.13

0.16

19.46

45.19

2.08

5.19

15 (10-25)

0.67

0.59

0.47

0.47

0.11

0.24

0.58

0.26

0.26

0.08

0.09

0.02

0.19

0.90

0.42

0.82

0.11

0.67

0.18

0.12

1.05 (0.83-1.32)

1.05 (0.88-1.26)

1.05 (0.91-1.21)

1.22 (0.97-1.55)

1.23 (1.04-1.47)

1.08 (0.96-1.22)

No clinical significant difference

associated with survival.

Complications and length of

stay are not influenced by

operation time

HR = hazard ratio; CI = confidence interval; DCD = donation after cardiac death; LOS = length of stay

Results: Thoracic organ transplant surgery

• 1 studie: in totaal 27 118 patiënten (dag vs nacht transplantaties)

16 573 harttransplantaties en 10 545 longtransplantaties

• Geen verschil in outcome

– Enkel toegenomen mortaliteit 90 dagen post longtransplant MAAR geen verschil in

mortaliteit 1 jaar postoperatief

Conclusion• De resultaten zijn inconclusief

• In de meerderheid van studies kon er geen verslechtering van

outcome bij studies uitgevoerd tijdens de nacht of in het weekend

• Mogelijke verklaringen hiervoor:I. Gespecialiseerde transplant teams tijdens wachten

II. Overdag mogelijks meer training van jonge chirurgen en residenten

III. Goede follow-up programma’s pre-operatief

IV. Operatie tijd wordt bepaald door beschikbaarheid van donor orgaan

V. Compensatie door meer ICU-opnames

VI. Rustigere omgeving, minder onderbrekingen ‘s nachts, fysiologische verandering

=> Omdat het onmogelijk is om de beschikbaarheid van een donor orgaan te

voorspellen, blijft transplantatie-heelkunde na de ‘kantoor’-uren een veilige optie