Supportive Care in Cancer Miroslav Tomíška Internal Medicine, Block 4 5th year students [USEMAP] 2 Supportive care in oncology nAntiemesis nTreatment of cancer pain nManagement of hematological toxicity nInfectious complications nMetabolic complications nNutrition support nPsychosocial support § [USEMAP] 3 Antiemesis Chemotherapy Induced Nausea and Vomiting CINV [USEMAP] Types of CINV 4 CINV type Description Acute 0-24 h Delayed 25-120 h (Day 2-5) Anticipated prior further chemo cycle Breakthrough despite prophylaxis Refractory not responding to treatment [USEMAP] 5 Risk factors for CINV § Cytotoxic agents Patient-based factors Emetogenic drug Young age < 50 yr Higher dose of the drug Female gender Combination of drugs History of vomiting CINV after prior chemo cycle Anxiosity Alcohol abstinence [USEMAP] 6 Classification of cytotoxic drug emetogenicity Classes of emetogenicity Probability of CINV without prophylaxis High > 90 % Moderate 30-90 % Low 10-30 % Minimal < 10 % Generaly emetogenic means the risk of CINV > 30 % [USEMAP] 7 Antiemetic drugs Class Generic names Half life hours 5HT3R inhibitors ondansetron granisetron palonosetron 3 9 40 NK1R inhibitors aprepitant netupitant rolapitant 9 96 120 Corticosteroids dexametasone Atypical antipsychotic olanzapin Prokinetic agents metoclopramide Anxiolytics alprazolam lorazepam [USEMAP] 8 Rules for antiemetic prophylaxis in chemotherapy treated patients nPrevention from the 1st cycle ‒in emetogenic chemotherapy (moderate to high risk) nUse of full defined doses af antiemetics ‒do not reduce the dose nCombined antiemesis recommended ‒dexamethasone is a routine part of combination ‒add anxiolytics in anxious patients ‒monotherapy for low-risk patients nOral formulation sufficient for prevention nModern antiemetics with long half life ‒potencially 1 dose for the whole cycle of chemotherapy n [USEMAP] Combined antiemetic prophylaxis regimens used according to total CINV risk of the patient 5HT3-inhibitor dexamethasone 5HT3-inhibitor dexamethasone alprazolam NK1-inhibitor 5HT3-inhibitor dexamethasone Three drug regimen for high risk of CINV NK1-inhibitor 5HT3-inhibitor dexamethasone alprazolam Olanzapin regimen as an alternative olanzapin palonosetron dexamethasone Routine 2-drug regimen for moderate risk patients Potencial regimen for the highest emetic risk / after failure olanzapin palonosetron dexamethasone NK1-inhibitor [USEMAP] 10 Akynzeo© capsules netupitant 300 mg / palonosetron 0.5 mg nFirst fixed 2-drug combination –both components with long half life nInhibits two main pathways of emesis after CT –covers both acute and delayed period, highly effective n1 capsule 1 hr prior to the start of CT –effective for the whole cycle nImproves compliance with antiemetic regimen –solves known gaps between guidelines and reality –decreases the risk of mistake nCost-effective despite of high charges [USEMAP] 11 Cancer pain management principles of therapy [USEMAP] 12 Chronic cancer pain characteristics two patterns: continuous or intermittent nMultidimensional phenomen –complex interaction between many factors –includes psychological factors –causes syndrome (rather than symptome in acute pain) nChronic pain may be a patogen itself –can facilitate progression of metastatic disease –negative predictor of survival –worsens quality of life nNeuropathic pain –damage to the nerves and surrounding tissues –pathological persisting type of pain, hyperesthesia –maladaptive response [USEMAP] 13 Principles of cancer pain management nDrug therapy is the cornerstone nPrescription on an around-the-clock basis –using analgesic ladder –use combinations of analgesic drugs nStrong opioids for increasing and moderate to severe pain nSpecific treatment for neuropathic pain –antiepileptics, anticonvulsants nRescue doses for breakthrough pain –rapidly acting formulations [USEMAP] 14 Analgesic ladder for cancer pain management nSTEP 1 nNon opioid analgetics ‒paracetamol ‒NSAIDs nAdjuvant (co-analgetics) ‒antidepresants, anxiolytics ‒anticonvulsants, gabapentinoids ‒corticosteroids ‒cannabinoids nSTEP 2 nWeak opioids (+- non-opioid / adjuvant) nSTEP 3 nStrong opioids (+- non-opioid / adjuvant) – § [USEMAP] 15 Weak opioids for cancer pain nTramadol –injection i.v., i.m., s.c. –oral drops, short acting, dosed by 4-6 hrs –oral slow-release tablets, dosed bid –combined with paracetamol in tablets nCodein –short-acting, dosed by 4-6 hrs nDihydrocodein –DHC Continus prolonged release tablets, dosed bid nOxycodon low dose [USEMAP] 16 Strong opioids for cancer pain management nMorphine –injection s.c., i.m. –oral immediate-release morphine (bioavailability 20-40 %) –slow-release tablets / capsules, dosed bid nFentanyl –TD patch (transdermal), be changed by 72 hrs –buccal tablets (rapid resorption) for breakthrough pain –intranasal spray (very rapid resorption) nBuprenorfin TD nHydromorhone oral (dosed bid, by 12 hrs) nOxycodone oral (dosed bid, by 12 hrs) n [USEMAP] 17 Recommendations for opioid therapy distinct pharmaco-dynamic differences between individuals nEffective dose is very individual ‒no ceiling effect to opioid dosing ‒side effects are usually limiting nDose of opioids needs to be titrated ‒morphine provide similar pain control as newer opioids ‒tolerance and physical dependence is predictable ‒different from psychological dependence nUndertreatment is common ‒uncontrolled pain may decrease cognition, similar to opioid side-effect (for drivers) nRisk of opioid accumulation in renal failure ‒buprenorfin kinetics preserved in renal insufficency n [USEMAP] 18 Recommendations for opioid therapy distinct pharmaco-dynamic differences between individuals nOpioids should be combined with ‒non-opioids (paracetamol, NSAIDs) ‒adjuvant drugs (antidepressants and others) nOpioid rotation ‒switch to different opioid in case of tolerance or side effects to improve effect and/or lower risk of toxicity ‒equianalgesic dose caculation nProphylactic laxatives ‒useful for many patients (allow opioid continuation) ‒combination of opioid with oral naloxone nUse of multiple opioids simultaneosly is inappropriate n [USEMAP] 19 Dose-limiting side effects of strong opioids no defined maximal doses for strong opioids nRespiratory depression ‒risk is minimal in adequate dose titration nConstipation and dry mouth ‒independent of dose nNausea and vomiting ‒usually transient, resolve within days nSedation, sleepiness, dizzinies nDelirium, confusion ‒dose-limiting side-effect nCutaneous pruritus [USEMAP] 20 Febrile neutropenia Management of sepsis [USEMAP] 21 Febrile neutropenia (FN) severe neutropenia increases the risk of infection §Fever + § §> 38.5 °C §> 38.0 °C > 1 hr Neutropenia < 0.5 *109/L severe neutropenia Not in all FN cases there is an infection. Criteria of FN may be fulfilled in other causes of fever, like drug fever etc, but infection cannot be excluded in limited time. Treatment should cover potential causes of infection (risk of rapid progression of infection within hours). [USEMAP] 22 Different risks of febrile neutropenia fufilling one or more characteristic features nHigh risk ‒hematological patients (leukemia) ‒expected to continue for more than 5 days ‒very severe neutropenia < 0.1 *109/L Hospital stay, i.v. broad spectrum antibiotics nLow risk ‒solid cancer patients ‒short period of neutropenia < 5 days ‒not very severe (above 0.1 *109/L) Outpatient, oral antibiotics [USEMAP] 23 Empirical antibiotic therapy in high-risk febrile neutropenia and sepsis nStart immediately after diagnosis ‒up to 1 hr after diagnosis ‒just after collection of blood for culture (2 sets) nBroad spectrum antibiotics i.v. ‒full dose recommended for severe infection cefepime + amikacin 1st choice in this dept add vancomycin if indicated risk of G+ infection meropenem + vancomycin in hemodynamic instability [USEMAP] 24 Antifungal therapy in high risk febrile neutropenia and sepsis nEmpirical antifungals ‒in high risk FN ‒persisting fever despite empirical antibiotics day 5-7 ‒progressive signs of infection nTreatment of possible/probable fungal infection ‒high-resolution CT of lungs (hallo sign) ‒dynamic increase in serum galactomannan ‒suspicion for ivasive pulmonary aspergillosis caspofungin or micafungin Echinocandin class voriconazole Azole antifungal class [USEMAP] 25 Diagnosis of sepsis positive blood culture not required §Infection + § §Documented nmicrobiologically –blood stream infection –urinary tract infection nclinically –pneumonia –soft tissue infection – SIRS nFever / hypothermia > 38.3°C / < 36°C nTachycardia > 90/min. ─in fever >100/min. nTachypnea > 20 bpm ─pCO2 < 4.2 kPa nLeukocytosis ─or leucopenia [USEMAP] 26 Primary site of infection in sepsis 14,364 patients, 28 ICUs, 8 countries lung soft tissue urinary tract other blood abdomen [USEMAP] 27 Sepsis continuum in disease progression Infection Sepsis Severe sepsis Septic shock Multiple organ failure Death [USEMAP] 28 Diagnosis of severe sepsis require signs of tissue hypoperfusion nHypotensis responsive to i.v. hydration ─systolic arterial pressure < 90 mmHg ─mean arterial pressure, MAP < 65 mmHg ─ nSerum lactate > 4 mmol/L ─normal range 0-2 ─partially depending on liver function § nOrgan dysfunction ─kidney funcion: oliguria < 0.5 ml/kg/hr (< 100 ml/3 hr) ─lung funcion: hypoxia, dyspnea ─central nervous system: delirium, somnolence, confusion [USEMAP] 29 Diagnosis of septic shock definition nSepsis induced hypotension, persisting after i.v. hydration ‒initial hydration at least 30 mL/kg for 3 hrs ‒2100 mL for 70 kg person in 3 hrs nThe goal in lactate elevation is to decrease lactate level (improve tissue perfussion) nVasopressors necessary for septic shock ‒norepinephrin is the first choice ‒MAP > 65 mmHg is the goal n [USEMAP] 30 CVP < 10 cmH2O MAP < 65 mmHg ScvO2 < 70 % Goal 65-90 mmHg Vasopressors Red cell transfusion Dobutamine Crystaloids Central venous + arterial cannula Goal 10-16 cmH2O Reached goals in sepsis Goal > 70 % 1. 2. 3. [USEMAP] 31 Metabolic complications in oncology [USEMAP] 32 Tumor lysis syndrome, TLS characteristics nAggresive malignancy ─Burkitt lymphoma ─acute leukemia ─many other aggresive/chemosensitive tumors nBulky disease (large tumor volume) ─high lactate-dehydrogenase (LD) nClinical situations ─mosty occurs after first doses of chemotherapy ─chemosensitive malignancies ─even after corticosteroids (ALL, high-grade lymphoma) ─rarely spontaneous TLS [USEMAP] 33 Diagnosis of TLS laboratory monitoring nHyperuricemia ─uric acid is final metabolite of nucleic acids ─uric acid precipitation in (in low pH) nRenal failure ─rapid onset within hours nHyperkalemia ─may rapidly increase from morning to evening ─bradyarrythmia, heart arrest, sudden death nHyperphosphatemia ─calcium phosphate precipitation (in high pH) nHypocalcemia [USEMAP] 34 Prevention of TLS before starting chemotherapy nPrehydration ─start at least 12 hrs before ─3-6 L/day (oraly + intravenously) ─high urine output (> 100 mL/hr) prior to chemo ─combined with furosemide in older/cardiac patients nAllopurinol pretreatment ─start 24 hrs before starting chemo ─300-600 mg/day (reduction in renal insufficiency) ─does not treat preexisting hyperuricemia ─risk of drug-drug interactions ─risk of xanthine nephropathy ─ [USEMAP] 35 Urate oxidase enzyme in TLS rasburicase, recombinant urate-oxidase nConversion of uric acid to allantoin ─10times more soluble than uric acid nReduces preexisting hyperuricemia ─in contrast to allopurinol nRasburicase i.v. infusion ─plasma uric acid level rapidly decreases within 4 hrs ─single dose 6 mg commonly sufficient ─repeat as necessary ─risk of anaphylaxis (< 1 %) [USEMAP] 36 Monitoring of TLS according to the risk nTwice daily in patients at high risk ─diuresis (goal > 100 mL/hr) ─biochemistry (kreatinin, K, P, Ca) nAsymptomatic hypocalcemia should not be treated ─risk of calcium-phosphate precipitation ─alcaliniaition of urine not recommended [USEMAP] 37 Hypercalcemia in malignancy characteristics nPathophysiology in oncology –osteolytic metastases (osteoclast activity) –parathormone-related protein produced by cancer nSymptoms –osmotic diuresis causing dehydration –anorexia, nausea, vomiting –constipation, sometimes severe –confusion, central nervous system dysfunction l [USEMAP] 38 Treatment of hypercalcemia in malignancy at ICU nIntravenous hydration ‒saline infusion 200-300 mL/hr ‒hypovolemia exacerbates hypercalcemia nCalcitonin ‒rapidly acting in 4-6 hrs, tachyphylaxis after 48 hrs nBisphosphonates (more potent than calcitonin) ‒zoledronate, pamidronate ‒maximal effect in 48-96 hrs (2-4 days) ‒potential nephrotoxicity ‒used up to kreatinin 400 umol/L nDisease-specific approach ‒treatment of underlying disease [USEMAP] 39 SIADH in oncology Syndrome of inappropriate ADH secretion nPathophysiology –ADH caused water retention (usually mild) –secondary increase of natriuresis (natriuretic hormones) –euvolemic hyponatremia nLaboratory abnormalities –hyponatremia (may be asymptomatic) –low plasma osmolality (hypoosmolar hyponatremia) –urine Na concentration > 20 mmol/L (natriuresis) nClinical features –asymptomatic hyponatremia is a common feature –apetite loss, headache, dizzinies, muscle weakness –no oedema [USEMAP] 40 Etiology of SIADH in oncology nUnderlying cancer –lung cancer (SCLC) –mesothelioma –oropharyngeal, gastric, pancreatic cancer –malignant lymphoma nDrugs as a side effect –antidepressants (mainly SSRI) –antiepileptics –antipsychotic agents –cyclophosphamide, ifosfamide, vincristin [USEMAP] 41 Treatment of SIADH nWater restriction ‒to 800-1000 mL daily nFurosemide ‒eliminates more water than sodium nSodium chloride infusion ‒normal saline (0.9 % solution) ‒slow gradual correction of natremia ‒not faster than by 0.5-1 mmol Na in 1 hour ‒rarely hypertonic saline (3% solution) nVasopresin receptor antagonists ‒acting on renal tubuli blocking V2R [USEMAP] 42 Nutrition support in cancer [USEMAP] 43 Diagnosis of malnutrition is based on simple clinical findings nUnwanted weight loss > 10 % per 6 months –prognostically different from weight reduction –also applies to overweight and obese patients nDecreased BMI –interpretation depends on age and gender nInsufficient food intake ‒less than 60 % of usual intake more than 10 days nNutrition impact symptoms ‒increase risk and probability of reduced food intake nSerum albumin is not a reliable marker [USEMAP] 44 Median overall survival in cancer patients in months, according to baseline weight loss and BMI n=8160 14.2 3 4.7 4 7.1 4.1 3.7 4.7 4.8 8.1 8.1 6.2 5.4 4.4 9.2 6.8 6.7 10.7 11.9 10.5 10.6 7.8 21.5 15.7 13.5 8.4 19.9 13.1 10.2 8.1 6.1 4.7 17.3 11.3 7.5 6.2 4.4 BMI 28 25 22 20 WL 2.5 % 6 % 11 % 15 % Martin L…Baracos V. J Clin Oncol 2015; 33:90-99. [USEMAP] 45 Grading of weight loss in cancer patients worsening prognosis through grades 1-4 1 3 4 4 3 4 4 4 4 3 3 3 4 4 3 3 3 2 2 2 2 3 0 1 1 3 0 BMI 28 25 22 20 WL 2.5 % 6 % 11 % 15 % BMI 28 25 22 20 WL 2.5 % 6 % 11 % 15 % Martin L…Baracos V. J Clin Oncol 2015; 33:90-99. [USEMAP] 46 Median overall survival in cancer patients by grading of weight loss, n=8160 Martin L … Baracos V. J Clin Oncol 2015; 33:90-99. months [USEMAP] Interpretation of BMI for diagnosis of underweight low BMI alone should not be classified as malnutrition 47 Age 18-25 yr Age 25-65 roků Age > 65 roků BMI muži 19.0 20.5 22.0 BMI ženy 18.5 20.0 22.0 Example: BMI below 22 kg/m2 in seniors is in the range of underweigt and may support the diagnosis of malnutrition [USEMAP] High correlation of Mid Arm Circumference, MAC with BMI, n=1561 TMP30 2 Arm Circumference cm BMI kg/m2 Powell-Tuck, Hennessy, Clinical Nutrition 2003, str.307-312 45° Change of 1 BMI unit (3 kg for 173 cm height) reflects 1 cm of MAC 3 mm change of MAC reflects change 1 kg in body weight Applies to mid stature 173 cm (1.732 = 3,0) There is approx. 5 unit difference between MAC and BMI [USEMAP] Mid Arm Circumferencer, MAC cut-off values for diagnosis of malnutrition 49 OP Normal (median) cm Mild malnutrition cm Severe malnutrition cm Males 31.0 26.0 23.0 Females 30.0 25.0 22.0 Applies to mid stature around 173 cm. Excellent parameter in fluid retention, edema, ascites. [USEMAP] 50 Cancer cachexia is characterized by metabolic abnormalities with systemic inflammation in many, but not all patients, progressive loss of skeletal muscle mass is crucial Death Early metabolic changes IL-6 CRP albumin > 5-10 % Weight loss < 5% Systemic inflammation Anorexia Performance status Survival < 3 mo > 30 % > 20-30 % Cachexia Refractory cachexia Precachexia Glasgow Prognostic Score, GPS, range 0-2 points CRP > 10 mg/L Albumin < 35 g/L Score 1-2 points (in the absence of infection) reflects systemic inflammation, cancer cachexia and poor prognosis [USEMAP] Muscle area by CT at L3 level enables calculation of total body muscle mass 51 [USEMAP] Total energy requirements in cancer patients 52 Common low physical activity 25-30 kcal/kg/Day 1.4 * BEE Higher physical activity mostly younger pts. and males 30-35 kcal/kg/Day 1.5 * BEE Malnutrition, after weight loss mostly younger pts. and males 35-40 kcal/kg/Day 1.6 * BEE Expression per kilo BW applies to normal weight patients (normal BMI). Corrected weight is used for overweight and underweight (to the middle between Ideal BW (BMI 22 for mid age, 24 for seniors) and Actual BW. [USEMAP] Protein requirements in cancer patients delivery of increased needs in cancer is safe 53 Mild / moderte malnutrition 1.2-1.5 g/kg/Day Severe malnutrition 1.5-2.0 g/kg/Day Renal isufficiency 1.0-1.2 g/kg/Day Expression per kilo BW applies to normal weight patients (normal BMI). Corrected weight is used for overweight and underweight (to the middle between Ideal BW (BMI 22 for mid age, 24 for seniors) and Actual BW. [USEMAP] 54 Dietary counselling in cancer patient with anorexia/nausea nReleive unnecessary dietary restrictions nTreat nutrition impact symptoms –pain, nausea, anorexia, diarhea, constipation nEat small portions 5-6 times a day nKeep variety of foods nTake energy dense foods –increase fat intake nIncrease protein intake nEasy access to food snacks nAttractive serving of meals [USEMAP] 55 Oral Nutritional Supplements, ONS ready to use for sipping, 125-300 mL/can nComplete formulas for oral intake –high content of energy, proteins, vitamines –specific composition (omega-3 fatty acids) nLiquid or creme consistency nCans 125 ml, 200 ml, 220 ml, 300 ml nMany different tastes nEasy used in dental and swallowing problems nEasily digestable nSuccess with ONS depends on adequate motivation and individual approach [USEMAP] Classification of ONS Category Characteristic High Protein 20 g proteins / can High Energy 2 kcal / mL Small volume 125 ml, concentrated up to 3.2 kcal / ml Large volume 300 ml, up to 600 kcal / can Diabetic formula low glycemic index Omega-3 PUFA 0.75-1 g EPA / can Muscle support HMB, high protein / vitamin D [USEMAP] C:\Users\Miroslav\Pictures\PRÁCE\KNIHA 2017\DSC_0363.JPG Fine bore NG tube introduced by guidewire for nasogastric feeding Importance of fixation to face Polyuretan material for use up to 3 months [USEMAP] 58 > medical 005 Percutaneous endoscopic gastrostomy, PEG [USEMAP] Classification of products for tube feeding Category Characteristic Signed Standard 1.0 kcal / mL Standard Energy 1.5 kcal / mL (2 kcal / mL) 1500-2000 kcal / 1 L Energy High Protein 75-100 g proteins / 1 L HP Containing fibre 15 g fibre / 1L Fibre Diabetic formula low glycemic index contains soluble fibre Dia-, Dib- Glu- Omega-3 PUFA 2 g EPA / daily dose of energy Muscle support hydroxy-methyl-butyrate, HMB high protein and vitamin D [USEMAP] 60 Total parenteral nutrition (TPN) in cancer patients nEnteral nutrition cannot be used ‒bowel obstruction and other contrasindications nSurvival is more limited by malnutrition than progression of cancer nLife expectancy > 3 months ‒only patients surviving more than 2 mo profit from PN nPerformance status KPSI > 50, ECOG 0-2 ‒ability to walk even upstairs nFamily consensus, good background nStart only after meticulous deliberation ‒decision should not come from despair ‒PN should not prolong suffering [USEMAP] 61 Supplemental parenteral nutrition, Suppl PN new modality of nutrition support in cancer patients § Potential indication nInsufficient food intake ‒inability to deliver more nutrients through GI tract ‒signs of malabsorption (diarrhea) nContinuing weight loss ‒despite oral nutritional intervention with ONS nMalnutrition has not been severe so far nAdvanced cancer, but death is not imminent ‒cancer is not rapidly progressive nFor multimodal paliative care § [USEMAP] 62 Advantages of supplemental PN nPartially preserved enteral intake ‒supporting bowel function nLower amount of i.v. nutrients ‒lower side effects (hyperglycemia etc.) ‒lower risk of canulla infection ‒shorter time of delivery nPatient need not take PN each day ‒depending on oral intake and body weight ‒free days from PN nHelps to keep body weight / muscle mass nImprovement of Quality of Life § [USEMAP] PICC, Peripherally Inserted Central Catheter tip of catether in superior vena cava § 63 [USEMAP] Nutriflex Omega Special 1250 ml 3-chamber bag 1475 kcal 6100 kJ Aminoacids 70 g Glucose 180 g Fat 50 g EPA+DHA 3.1 g 64 [USEMAP] SMOF Kabiven 986 ml for supplemental PN 65 Content 1100 kcal 4600 kJ AA 50 g Glucose 125 g Fat 38 g 4-component fat emulsion S soya M MCT O oliv oil F fish oil [USEMAP] C:\Users\Miroslav\Pictures\PRÁCE\KNIHA 2017\DSC_0032.JPG Preparation of „All in one“ admixture in hospital pharmacy AiO [USEMAP] C:\Users\Miroslav\Pictures\PRÁCE\KNIHA 2017\DSC_0289.jpg AiO bag, individualized dose of nutrients for 24 hr C:\Users\Miroslav\Pictures\PRÁCE\KNIHA 2017\DSC_0287.jpg [USEMAP] New mixture of vitamins Viant® contains all 13 vitamins Vitamin Unit Requirement iv. Viant lag. B1 Thiamine mg 6 6 B2 Riboflavin mg 3.6 3.6 B3 Nikotinamidum mg 40 40 B5 Ac.pantothenicum mg 15 15 B6 Pyridoxin mg 6 6 B7 Biotin mg 60 60 B9 Acidum folicum mg 600 600 B12 Cyanokobalamin mg 5 5 C Ascorbic acid mg 200 200 [USEMAP] New mixture of vitamins Viant® contains all 13 vitamins Vitamin Unit Requirement iv. Viant lag. A Retinol equivalent mg 800-1000 1000 D3 Cholecalciferol mg 20 5 E Tocoferol-a eqival. mg 10 9.1 K1 Phytomenadion mg 150 150 [USEMAP] Nutryelt® new composition contains 9 trace elements Trace element Unit Requirement iv. Nutryelt Zn Zink mg 3-6.5 10 Se Selenium mg 60-100 70 Fe Iron mg 1,2 1 Cu Copper mg 300-500 300 Mn Manganese mg 60-100 55 F Fluor mg 950 950 I Iodine mg 130 130 Mo Molybdenum mg 19 20 Cr Chromium mg 10-20 10 [USEMAP] 71 The end [USEMAP]