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Anesthetic Management of the Cancer Patient

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sharon philips

on 8 July 2013

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Transcript of Anesthetic Management of the Cancer Patient

Anesthetic Management
of the Cancer Patient

Discuss surgical and anesthetic impacts on immunosuppression, which can lead to cancer recurrence

Review key elements of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC)

Identify implications for practice

Surgical and Anesthesia-mediated Immunosuppression
Objectives
Cancer Growth & Recurrence: Implications for Anesthesia
Always strive to maintain:
Normothermia
Glucose control
Normotension
Surgical Stress Response
Procedural Factors
Cell-mediated immunosuppression d/t inhibition of natural killer (NK) cells

Directly related to degree of surgical trauma and tissue damage

Lasts up to 1 week after surgery
Sharon Philips
Immunosuppression
by Non-pharmacologic means
Pain
Stress
Inflammation
Hypotension
Hypothermia
Unneeded transfusions
Neuroendocrine system & HPA Axis
Transfusion-related
immune modulation (TRIM)
Volatile Agents
Lymphocytic apoptosis
Decreased NK cell cytotoxicity
Altered NK cell-mediated release of cytokines
Opioids
Immunosuppression by
Pharmacologic means
Volatile agents + Opioids
Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy
Transfused patients experience immunosuppression:
Increased nosocomial and postop infections
Increased cancer recurrence
Improved survival rates s/p transplant

Mechanism
Decrease NK cell function
Altered ratio of helper:suppressor T lymphocytes
Decreased lymphocyte blastogenesis
Down-regulation of immune system
What is HIPEC?
HIPEC: Hemodynamics
Massive fluid shifts
Insensible loss + blood loss + albumin loss

Coagulopathy develops
Increased: INR, PTT
Decreased: ATIII, fibrinogen, platelet count

Transfusion (PRBC or FFP) often required
Intraop: ~ 50% of cases
Postop: ~ 33% of cases
Chemotherapy Agents
Oxylipatin
5% glucose mixture: hyperglycemia/hyponatremia
laryngeal and pharyngeal dysesthesias

Mitomycin C
Nephrotoxicity and pulmotoxicity

Doxirubicin
Arrhythmias and cardiomyopathy

Cisplatin
Peripheral neuropathy and renal failure
Pulse-less amiodarone-refractory VTach
d/t loss of magnesium and QT prolongation
Neuroendocrine system & HPA Axis modification
Pain
Stress
Inflammation
Hypotension
Hypothermia
Hyperglycemia
Avoid Unnecessary
Blood Transfusions
Restrictive transfusion policy:
Hgb 7-8.5 G/dL

Must be case-by-case

Strategies:
Use cell saver blood
Maintain normothermia
Consider pre-op recombinant EPO
Reduce unnecessary blood draws
NSAIDS for the Cancer Patient
Reduce COX-2 inflammatory pathway and reduce opioid consumption

Pre-operative Ketorolac
Retrospective study of mastectomies from 2003-2008 (n=327)
Ketorolac group = 5-fold reduction in relapse (Forget, et al., 2010)
Regional Anesthesia
Beta Blocker Therapy
Blocks noxious input to CNS and reduces the stress response
Helps avoid potential negative results of volatile agents and reduce opioid requirement
Studies:
[2012] Reduced length of stay (16.08, 21.58 days) and prolonged length of survival (95.9, 70.4 months)
[2006] Risk of recurrence 57% lower in epidural group
[2006] Increased length of cancer-free survival (24 months: 94% vs 82%; 36 months: 94% vs 77%)
Several observational studies show that patients taking beta blockers have reduced cancer development

Early research shows that non-selective beta antagonists (propranolol) diminish the stress response and abolish the pro-metastatic effect of norepinephrine

Propanolol + COX Inhibitor = synergistic block of cell-mediated immunosuppression
Implication for Practice:
Lines & Labs
Lines:
Always: large bore IV access
Often: arterial line
Sometimes: central line + CVP monitoring

Labs:
Metabolic acidosis/respiratory derangements
Monitor Hgb/Hct
Consider DIC screen
Consider ACT (bedside monitoring)
Implications for Practice:
Aggressive fluid administration
Close monitoring of UOP. If UOP drops:
Loop diuretic (Lasix)
Osmotic diuretic (Mannitol)
Cisplatin: Consider Na Thiosulfate infusion
Check/replace electrolytes (K+, Ca+, Mag)
Implications for Practice:
Fluids & Blood
Fluids:
Average 12ml/kg/hr
Crystalloid vs colloid
Consider albumin
Hespan often avoided d/t coagulopathies

Bleeding:
Cell saver (limit use of banked blood)
Coagulopathic patient: First-line is FFP
Know institutional transfusion policy
Management of HIPEC Phase
Increased abdominal pressure:
Decreased venous return
Increased splanchnic resistance
Displacement of diaphragm
Decreased FRC
Increased mean airway pressures

Goal: maintain minute ventilation without high mean airway pressures
Temperature Regulation
Cytoreduction [COLD] phase:
Bair Hugger + fluid warmer
Consider letting temp drift as low as 35 C before HIPEC initiated

HIPEC [HOT] Phase:
Cooling blanket, chilled IVF, forced air warmer on ambient setting
Consider permissive hyperthermia (39-40 C)
Hypermetabolic state:
Increased O2 demand, HR, ETCO2
Metabolic acidosis
Pain Management
Standard:
Intraop: fentanyl + dilaudid
Postop: sometimes morphine PCA

Alternative:
Thoracic epidural analgesia
Reduced ICU days, ventilator time, & consumption of opioids. N=20. (Mahran & Thabet, 2012)

Implications:
Assess for pre-op coagulopathy
Monitor for epidural hematoma
Cancer Growth
Patients who undergo surgery with GA have greatly increased rates of unrelated cancers c/t the predicted rates for their population

N = 13, 488. Augmentation mammoplasty. 21% increased risk of any cancer within 12 years; doubled risk of leukemia, stomach CA, & brain CA (Brinton, et al., 2001).

Occult cancers are common, with healthy people concealing cancers that never become clinically active [autopsy studies]
References
Algazi, M., Plu-Bureau, G., Flahault, A., Dondon, M., & Le, M. (2004). Could treatments with beta-blockers be associated with a reduction in cancer risk? Rev Epidemiol Sante Publique, 52(1), 53-65.
Arain, M. & Buggy, D. (2007). Anesthesia for cancer patients. Current Opinion in Anesthesiology, 20, 247-253.
Bell, J., Rylah, B., Chambers, R., Peet, H., Mohamed, F., Moran, B. (2012). Perioperative management of patients undergoing cytoreductive surgery combined with heated intraperitoneal chemotherapy for peritoneal surface malignancy: A multi-institutional experience, Annals of Surgical Oncology, 19, 4244-4251. DOI 10.1245/s10434-012-2496-y
Benish, M., Bartal, I., Goldfarb, Y., Levi, B., Avraham, R., Raz, A., & Ben-Eliyahu, S., (2008). Perioperative use of B-blockers and COX-2 inhibitors may improve immune competence and reduce the risk of tumor metastasis. Annals of Surgical Oncology, 15(7), 2042-2052.
Biki, B., Macha, E., Moriarty, D., Fitzpatrick, J., Sessler, D., & Buggy, D. (2008). Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis. Anesthesiology, 109(2), 180-187. doi: 10.1097/ALN.0b013e31817f5b73
Bovill, J. (2010). Surgery for cancer: Does anesthesia matter? Anesthesia-Analgesia, 110(6), 1524-1526. DOI: 10.1213/ANE.0b013e3181d8d183
Exadaktylos, A., Buggy, D., Moriarty, D., Mascha, E., & Sessler, D. (2006). Can anesthetic technique for primary breast cancer surgery affect recurrence of metastasis? Anesthesiology, 105(4), 660-664.
Forget, P., Vandenhende, J., Berliere, M., Machiels, J., Nussbaum, B., Legrand, C., & Kock, M. (2010). Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis, Anesthesia-Analgesia, 110(6), 1630-1635.
Goldstein, M. & Macitelli, L. (2011). Surgery and cancer promotion: are we trading beauty for cancer? The Quarterly Journal of Medicine, 104, 811-815. doi:10.1093/qjmed/hcr039
Kurosawa, S. (2012). Anesthesia in patients with cancer disorders, Current Opinion in Anesthesiology, 25(3), 376-384. DOI:10.1097/ACO.0b013e328352b4a8
Lindholm, M., Granath, F., Eriksson, L., & Sandin, R. (2011). Malignant disease within 5 years after surgery in relation to duration of sevoflurane anesthesia and time with bispectral index under 45, Anesthesia-Analgesia, 113(4), 778-783. DOI: 10.1213/ANE.0b013e31821f950e
Mahran, E. & Thabet, T. (2012). Comparative study between continuous epidural infusion vs intravenous patient controlled analgesia (PCA) to control post-operative pain after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), Ain Shams Journal of Anesthesiology, 5(1), 79-87.
National Cancer Institute. (2012). Cancer trends progress report - 2011/2012 update. U.S. National Institutes of Health. Retrieved from http://progressreport.cancer.gov/directorsmessage.asp
Outcomes Research Consortium. (2012). Regional anesthesia and breast cancer recurrence. Retreived from http://clinicaltrials.gov/show/NCT00418457
Owusu-Agyemang, P., Arunkumar, R., Green, H., Hurst, D., Landoski, K., & Hayes-Jordan, A. (2012). Anesthetic management and renal function in pediatric patients undergoing cytoreductive surgery with continuous hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin. Annals of Surgical Oncology, 19, 2652-2656. Doi: 12.1245/s10434-012-2319-1.
Palm, D., Lang, K., Niggemann, B., Drell, T., Masur, K., Zaenker, K., & Entschladen, F. (2005). The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by B-blockers. International Journal of Cancer, 118, 2744-2749.
Perron, L., Bairati, I., Harel, F., & Meyer, F. (2004). Antihypertensive drug use and the risk of prostate cancer. Cancer Causes Control, 15(6), 535-541.
Raghavan, M. & Malik, P. (2005). Anemia, allogenic blood transfusion, and immunomodulation in the critically ill. Chest, 127(1), 295-307.
Raspe, C., Piso, P., Wiesenack, C., & Bucher, M. (2012). Anesthetic management in patients undergoing hyperthermic chemotherapy. Current Opinion in Anesthesiology, 25, 348-355. Doi: 10.1097/ACO.0b013e32835347b2.
Sacerdote, P. (2006). Opioids and the immune system. Palliative Medicine, 20, s9-s15.
Schmidt, C., Creutzenberg, M., Piso, P., Hobbhahn, J., & Bucher, M. (2008). Perio-operative anesthetic management of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, Journal of the Association of Anaesthetists of Great Britain and Ireland, 63, 389-395. doi:10.1111/j.1365-2044.2007.05380.
Tavare, A., Perry, N., Benzonana, L., Takata, M., & Ma, D. (2012). Cancer recurrence after surgery: direct and indirect effects of anesthetic agents, International Journal of Cancer, 130, 1237-1250.
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HIPEC
Massive fluid losses & shifts
Risk of acute renal failure
Electrolyte imbalances
Temperature regulation
Coagulopathy
Multimodal pain management

Our impact extends beyond the OR
Actively seek out emerging evidence
Immunosuppression:
HPA Axis
Highly immunosuppressive:
Morphine, fentanyl, remifentanil, methadone, codeine

Less immunosuppressive:
Buprenorphone, hydromorphone, oxycodone, tramadol
Immunosuppression: COX-2
Current, multi-center NIH study:
Stage I-III patients undergoing mastectomy or isolated lumpectomy + axillary dissection
Group I - thoracic epidural or paravertebral anesthesia/analgesia
Group II - GA (Sevo) + morphine

Assessing rate of recurrence/metastasis over 10 years (2007-2017)
(Kurosawa, 2012; Gottschalk, et al., 2010; Arain & Buggy, 2007)
(Altman, et al., 2010;
Brasky, et al., 2009;
Brinton, et al., 2001;
Goldstein & Macitelli, 2011;
McLaughlin, et al., 1998;
Nauman, et al., 2008)
(Bovill, 2010; Goldstein & Macitelli, 2011; Goldfarb & Ben-Eliyaho, 2006; Shakhar & Ben-Eliyaho, 2003)
(Outcomes Research Consortium, 2012)
Treatment for surface peritoneal malignancies
Extends life expectancy by 16-24 months c/t traditional systemic therapy

Procedure:
Cytoreducion surgery
3-5 L of heated chemotherapy (42-43 degrees C) instilled into peritoneum
Chemo circulates for 30-120 minutes
Total OR time: 4-11.5 hours (average 5-6 hours)
HIPEC
(Raspe, et al., 2012; Schmidt, et al., 2008)
(Bell, et al., 2012; Raspe, et al., 2012; Schmidt, et al., 2008)
(Bell, et al., 2012; Mahran & Thabet, 2012; Raspe, et al., 2012; Schmidt, et al., 2008; Owusu-Agyemang, 2012)
(Dougenis, et al., 2001; Rahgavan & Malik, 2005; Webber, Jabour & Martin, 2008)
(Bovill, 2010; Kurosawa, 2012)
(Bovill, 2012; Kurosawa, 2012; Sacerdote, 2006)
Surgery + GA can trigger microscopic cancers which typically remain dormant to convert to active cancer or recurrence
Increased susceptibility to cancer growth
(Algazi, et al., 2004; Benish, et al., 2008; Biki, et al., 2006; Dougenis, et al., 2001; Exadaktylos, et al., 2006; Forget, et al., 2010; Gottschalk, et al., 2012; Palm, et al., 2006; Perron, et al., 2004; Rhagavan & Malik, 2005; Weber, Jabbour, & Martin, 2008;
Summary
Inflammation is the "fuel that feeds the flames"
Body's response to stress
Increased cortisol
Impaired cellular immune responses
Full transcript