Dealing with the haemato-Dealing with the haemato-oncology patient in intensive careoncology patient in intensive care

Dr Tim Wigmore FRCA, FJFICMDr Tim Wigmore FRCA, FJFICM

Consultant Intensivist, Royal Marsden Consultant Intensivist, Royal Marsden HospitalHospital

ICM at the MarsdenICM at the Marsden

11 Level 3 beds in Chelsea11 Level 3 beds in Chelsea 2 HDU beds in Sutton2 HDU beds in Sutton 900 admissions per year900 admissions per year

– 70% elective/emergency surgical70% elective/emergency surgical– 30% mix of various medical 30% mix of various medical

oncologyoncology– 5-6% Haemato-oncology5-6% Haemato-oncology

Outcomes for Haemato-oncology Outcomes for Haemato-oncology patientspatients

Prognostic indicatorsPrognostic indicators General Admission strategyGeneral Admission strategy Bone Marrow Transplant patientsBone Marrow Transplant patients Prognostic indicatorsPrognostic indicators Common problems with BMTsCommon problems with BMTs Admission strategy for BMTsAdmission strategy for BMTs

Improving outcomesImproving outcomes

General trends for the haemato-General trends for the haemato-oncology patientoncology patient

ICU MortalityICU Mortality

Relative survival from NHLRelative survival from NHL

Relative survival from multiple myelomaRelative survival from multiple myeloma

Source :CR-UK

Relative survival from leukamiaRelative survival from leukamia

Source :CR-UK

ICU Mortality – Bone Marrow ICU Mortality – Bone Marrow TransplantsTransplants

Azoulay 2009

RMH ICU Haemato-oncology data RMH ICU Haemato-oncology data 2005-20092005-2009

1 in 4 Haem-Onc Patients need ICU1 in 4 Haem-Onc Patients need ICU n=199n=199 43% (n=87) post bone marrow 43% (n=87) post bone marrow

transplanttransplant Apache 24.7 +/-7.6Apache 24.7 +/-7.6 Mortality 38.2% (ICU) Mortality 38.2% (ICU)

51.4% (Hospital)51.4% (Hospital)

ICNARC data for Haem-Onc patients ICNARC data for Haem-Onc patients 1995-20071995-2007

Comparative Haem-Onc Comparative Haem-Onc MortalityMortality

What has changedWhat has changed

New drugsNew drugs– GCSFGCSF– New antibiotics and antifungalsNew antibiotics and antifungals

New techniquesNew techniques– Less myeloablative techniquesLess myeloablative techniques– More autologous transplantsMore autologous transplants

Changes in ICU careChanges in ICU care– Early ICU admissionEarly ICU admission– GDTGDT– Less therapeutic nihilismLess therapeutic nihilism

Debunking the mythsDebunking the myths

Disease statusDisease status NeutropeniaNeutropenia SepsisSepsis Recent chemotherapyRecent chemotherapy Mechanical VentilationMechanical Ventilation

Disease prognosis does not affect ICU survivalDisease prognosis does not affect ICU survival

Massion et al, CCM 2002

Neutropenia does not affect ICU survivalNeutropenia does not affect ICU survival

Darmon et al , ICM 2002

Sepsis has a similar ICU outcome in Cancer and non-Sepsis has a similar ICU outcome in Cancer and non-Cancer patientsCancer patients

Pene et al, CCM 2008

Use of chemotherapy prior to admission does not affect ICU Use of chemotherapy prior to admission does not affect ICU

survivalsurvival

Vandijck et al, ICM 2008

Ventilation Ventilation in the first 24hrsin the first 24hrs does not affect survival in does not affect survival in ICUICU

• ICNARC review of haemato-oncology ICU admissions

IMV within 24 hours of admission not associated with increased mortality after adjustment for other prognostic factors

70.2% of intubated patients died in hospital

45.3% of non-intubated died in hospital

RMH ICU results for patients ventilated in the RMH ICU results for patients ventilated in the first 24 hoursfirst 24 hours

N=81N=81 ICU mortality 58.8%ICU mortality 58.8% Hospital mortality 64.7%Hospital mortality 64.7%

6 month mortality 72.5%.6 month mortality 72.5%.

What What does does predict predict outcomes ?outcomes ?

– Organ failure Organ failure √√– Progression of organ failure Progression of organ failure √√

Organ failureOrgan failure– High initial organ failure scoreHigh initial organ failure score– Progress of organ dysfunction Progress of organ dysfunction – Development of OF post admissionDevelopment of OF post admission

Initial SOFA scores predict Initial SOFA scores predict survivalsurvival

Cornet et al, Eur J Haematol 2005

Progress of OF predicts survivalProgress of OF predicts survival

Lecuyer et al, CCM 2007

Development of Development of latelate Organ Failures predicts death Organ Failures predicts death

Time refers to time from admission to development of organ failure

Black dot = Non survivor

Open triangle = survivor

OF progression predicts death but not OF progression predicts death but not foolproof !foolproof !

Lamia et al ICM Oct 2006

Above the line = Deteriorating organ statusBlack dot = SurvivorClear dot = Non survivor

Scoring systemsScoring systems

Most scoring systems fare badlyMost scoring systems fare badly Tendency to underestimate Tendency to underestimate

mortalitymortality Accurate at extremesAccurate at extremes ICMM designed specifically for ICMM designed specifically for

cancer patientscancer patients

So…who should I admit to ICU ?So…who should I admit to ICU ?

Survival has improved for critically ill Survival has improved for critically ill cancer patientscancer patients

Classic predictors of mortality have Classic predictors of mortality have lost much of their valuelost much of their value

The characteristics of the malignancy The characteristics of the malignancy are not associated with ICU mortalityare not associated with ICU mortality

Scoring systems do not perform wellScoring systems do not perform well Mortality depends on organ failures at Mortality depends on organ failures at

presentation and at 3 dayspresentation and at 3 days

So…who should I admit to ICU ?So…who should I admit to ICU ?

Request for admission to ICU

Bedridden patients

Very poor disease prognosis

Patient refuses

No ICU admission

All other patients

4 day trial admission with full treatment with re-assessment on day 5

Prev untreated

Tumour lysis

Patients in remission

Full ICU management

Bone marrow transplantationBone marrow transplantation

50-60,000/yr – Most autologous50-60,000/yr – Most autologous Most commonMost common

– Multiple myelomaMultiple myeloma– NHLNHL– AMLAML– HodgkinsHodgkins

Approx 15% end up in ICUApprox 15% end up in ICU

Bone marrow TransplantationBone marrow Transplantation

PreconditioningPreconditioning– ChemotherapyChemotherapy– RadiotherapyRadiotherapy– Ablative vs non-ablativeAblative vs non-ablative

Stem cell sourceStem cell source– AutologousAutologous– Allogeneic Allogeneic

CordCord Matched relatedMatched related Matched unrelatedMatched unrelated

Reasons for admission to ICUReasons for admission to ICU

RMH ICU BMT dataRMH ICU BMT data

N=87N=87 ICU mortality 36.8% ICU mortality 36.8% Hospital mortality 49.4%Hospital mortality 49.4% 6-month mortality 63.2%6-month mortality 63.2%

BMT prognosis in ICUBMT prognosis in ICU

Predictors of good outcomePredictors of good outcome– AutograftAutograft

– Younger ageYounger age

– Resp failureResp failure Pulmonary OedemaPulmonary Oedema Bacterial PneumoniaBacterial Pneumonia

– Ventilation for less than 7 Ventilation for less than 7 daysdays

Predictors of poor outcomePredictors of poor outcome– AllograftAllograft

GVHDGVHD Increasing HLA mismatchIncreasing HLA mismatch

– Increasing AgeIncreasing Age– Recurrent malignancyRecurrent malignancy– Resp failureResp failure

DAHDAH IPSIPS BOOPBOOP CMV, RSVCMV, RSV AspergillosisAspergillosis

– Ventilation for more than 7 Ventilation for more than 7 daysdays

Huynh et al. Outcome and Prognostic Indicators of Patients with Hematopoietic Stem Cell Transplants Admitted to the Intensive Care Unit

Invasive Ventilation and mortality for BMT Invasive Ventilation and mortality for BMT recipientsrecipients

Afessa, and Azoulay, Crit Care Clinics Jan 2010

So…which BMT do I admit to ICU ?So…which BMT do I admit to ICU ?

ICU admissionICU admission– Pre-engraftmentPre-engraftment– No recurrenceNo recurrence

ICU trialICU trial– Unknown disease statusUnknown disease status– Recurrence with available treatment optionsRecurrence with available treatment options

RefusalRefusal– Disease recurrence with no treatment optionsDisease recurrence with no treatment options– BedriddenBedridden– Severe GVHDSevere GVHD

InfectionInfection

Pre-engraftment (0-30 days)Pre-engraftment (0-30 days)– Neutropenia and breaks in mucocutaneous barriersNeutropenia and breaks in mucocutaneous barriers

BacteriaBacteria CandidaCandida AspergillusAspergillus

Early post engraftmentEarly post engraftment– Impaired cell mediated immunityImpaired cell mediated immunity

CMVCMV PCPPCP AspergillusAspergillus

Late post engraftmentLate post engraftment– Impaired cell mediated and humoral immunity (partic in allogeneic)Impaired cell mediated and humoral immunity (partic in allogeneic)

VirusesViruses HaemophilusHaemophilus StrepStrep TBTB

CXR cluesCXR clues

LobarLobar DiffuseDiffuse Acute intersititialAcute intersititial CavitatingCavitating

Upper lobesUpper lobes

Bacterial Bacterial OpportunisticOpportunistic ViralViral TB, Klebsiella, TB, Klebsiella,

Staph, NocardiaStaph, Nocardia TB, Klebsiella, TB, Klebsiella,

Meliodosis, Meliodosis, Aspergillus, Aspergillus, Pneumocystis, CMVPneumocystis, CMV

Investigation of Respiratory failureInvestigation of Respiratory failure

Respiratory failure in the BMT Respiratory failure in the BMT patientpatient

30 60 90

Virus CMV, RSV, Adenovirus, VZV, EBV

Bacteria Gram +ve or -ve Intracellular, Encapsulated

Fungi Candida Aspergillus, PCP Emerging fungal infections

Non- infectious

Pulm Oedema

DAH

Engraftment synd IPS COP, BO, Pulm GVHD

Infectious

Days since BMT0

NPPV in BMTNPPV in BMT

Possibly decreases mortality Possibly decreases mortality – Azoulay et al CCM 2001Azoulay et al CCM 2001– Afessa et al CCM 2003Afessa et al CCM 2003– Pene et al J Clin Oncol 06Pene et al J Clin Oncol 06

Small numbers in the trialsSmall numbers in the trials Requires early intervention and Requires early intervention and

acutely reversible causeacutely reversible cause Anecdotal experience at RMHAnecdotal experience at RMH

Other potential Other potential problems problems GvHDGvHD Tumour LysisTumour Lysis Veno-occlusive disease (VOD)Veno-occlusive disease (VOD) Blood product supportBlood product support

GvHDGvHD

Classic TriadClassic Triad Can affect lung alsoCan affect lung also Management via (more) Management via (more)

immunosuppressionimmunosuppression

Veno-occlusive diseaseVeno-occlusive disease

Occurs in first 21 days post TxOccurs in first 21 days post Tx Due to Hepatic endothelial damage from pre-Due to Hepatic endothelial damage from pre-

conditioningconditioning Thrombosis leads to Thrombosis leads to

– Weight gainWeight gain– HepatomegalyHepatomegaly– HyperbilirubinaemiaHyperbilirubinaemia– AscitesAscites

Diagnosis with DopplerDiagnosis with Doppler Defibrotide has drastically reduced incidence and Defibrotide has drastically reduced incidence and

mortalitymortality

Tumour LysisTumour Lysis

Typically following induction Typically following induction chemotherapy for leukaemia or chemotherapy for leukaemia or lymphomalymphoma

Predicted by an LDH>1500Predicted by an LDH>1500 Up to a third occur spontaneouslyUp to a third occur spontaneously

Causes release of purines, Causes release of purines, potassium and phosphatepotassium and phosphate

ConsequentConsequent– Life threatening arrhythmiasLife threatening arrhythmias– ARF (uric acid and calcium ARF (uric acid and calcium

phosphate deposition)phosphate deposition)

Purines from nucleic acids

Xanthine

Uric acid (Insoluble)

Allantoin (soluble)

Deposits in kidney leading to ARF Urate

Oxidase

Xanthine Oxidase

Rasburicase

Allopurinol

ProphylaxisProphylaxis– HydrationHydration– Allopurinol or rapspuricaseAllopurinol or rapspuricase– Avoid urine alkalinization (xanthines more insoluble Avoid urine alkalinization (xanthines more insoluble

in alkaline urine)in alkaline urine) TreatmentTreatment

– SymptomaticSymptomatic– Avoid correcting hypocalcaemia unless ECG Avoid correcting hypocalcaemia unless ECG

changeschanges– RasburicaseRasburicase– Filtration Filtration

Blood product supportBlood product support

All products must be irradiated All products must be irradiated – Risk of fatal GvHD from Tx T Risk of fatal GvHD from Tx T

lymphocyteslymphocytes All patients should have CMV –ve All patients should have CMV –ve

products (even if CMV +ve preTx)products (even if CMV +ve preTx)– If non available, leucodepleted red If non available, leucodepleted red

cells of platelets can be used in prev cells of platelets can be used in prev CMV +ve ptsCMV +ve pts

In conclusionIn conclusion

Outcomes are improvingOutcomes are improving Therapeutic nihilism is self fulfillingTherapeutic nihilism is self fulfilling

BUT….BUT…. Heavy users of resourceHeavy users of resource Trials of admission require a clear Trials of admission require a clear

understanding and a close understanding and a close relationship with the relatives and relationship with the relatives and haematologists !haematologists !

Early versus late admission to ICUEarly versus late admission to ICU

Larche et al ICM 2003

Bigger units get better Bigger units get better resultsresults Lecuyer et al, euro resp journal Lecuyer et al, euro resp journal

20082008