Complications of parenteral nutrition

Dr Alison CulkinLead Intestinal Failure Dietitian

St Mark’s HospitalPENG PN study day 2018

NCEPOD 2010

http://www.ncepod.org.uk/2010report1/downloads/PN_report.pdf

% of patients

No of patients

Good practice 19.5% 171

Metabolic complications

39.3% 249

Avoidable 49.4% 81

Inappropriately managed

15.5% 30

Session outline

•Catheter related bloodstream infections•Glucose & lipid abnormalities•Parenteral nutrition associated liver disease•Micronutrient deficiencies

Do you have a CVC complications protocol?

YesNo Don’t know

Catheter-related infection (CRI)

O’Grady et al (2011) Guidelines for the prevention of intravascular catheter-Related Infection, Clin Infec Dis, 52:e162

Localised Systemic

Infusate related

Catheter associated

Catheter related

Exit site infection

Tunnel infection

Cuff infection

In tunnelled CVC local infection is rarely associated with systemic infection

Exit site infection

Erythema or induration within 2cm of exit site in absence of bacteraemia

Cuff infection

Isolated infection affecting cuff

Tunnel infection

Erythema or induration > 2cm from exit site

Overgranulation

Granulation tissue at exit site

Treating CRBSI

Removal● Septic shock● Fungal & Staph Aureus infections● Positive blood cultures after 48 hours of treatment● Implanted port

Salvage● Targeted antibiotic therapy via CVC● Seek microbiology guidance● Optimum duration of therapy has not been determined● BIFA statement1

Removal Salvage

1 https://www.bapen.org.uk/pdfs/bifa/recommendations-for-crbsi-diagnosis.pdf

Prevention

Healthcare workers caring for patients with intravenous access devices should be trained and assessed as competent in consistently adhering to practices for the prevention of catheter related bloodstream infections

Loveday et al (2014) epic3 Guidelines, J Hosp Infect, 86 S1, S1

CVC related thrombosis

Affect 35-65% long term devices

● Often asymptomatic

Strategies which may influence incidence

● Avoid dehydration● Use the smallest size CVC possible● Minimise insertion site trauma● Right vs left side placement● Tip position● Tip integrity

Endothelial trauma

StasisPlateletadhesion

Loveday et al (2014) epic3 Guidelines, J Hosp Infect, 86 S1, S1O’Grady et al (2011) Guidelines for the prevention of intravascular catheter-Related Infection, Clin Infec Dis, 52:e162

Virchow’s triad

Reducing thrombosis

Cadman et al (2004) Clin Radiol, 59: 349

48% CVC tips too high on transfer

The risk of thrombosis is significantly increased with proximal SVC tip position

Catheter tip Thrombosis%

Proximal 42

Intermediate 5

Distal 3

Treatment optionsThrombolysis

● Alteplase +/- heparin

Mechanical interventions● Balloon angioplasty

● Venoplasty

● SVC filter

● Recannalisation

Surgical interventions● Thrombectomy

● Venous bypass

Pironi et al (2016) ESPEN Guidelines on chronic IF in adults, Clin Nutr, 35, 247

Session outline

•Catheter related bloodstream infections•Glucose & lipid abnormalities•Parenteral nutrition associated liver disease•Micronutrient deficiencies

HyperglycaemiaBlood glucose monitoring essential• Risk of hyperglycaemia in obese and diabetic patients can be reduced if

initial amounts of glucose in PN are <2g/kg/d until normoglycaemiaachieved1

Workshop case study • 125kg x 2g = 250g = 1000kcal

1. Barazzoni et al (2017) Clin Nutr, 36:355

Glycaemic control in non ICU

Olveira et al (2015) Nutrition, 31:58

N = 605BMI = 25.2±5.5

Kcal/kg = 25.1±5.7Days on PN 13±11

Hyperglycaemia(>10mmol/L)↑ Risk of death Malnourished

Older?Sicker as CRP ↑

& albumin ↓

Hypoglycaemia (<3.9mmol/L)Associated with

↓BMIPN durationHigh blood

glucose variabilityOlveira et al (2013) Diabetes Care, 36:1061

ESPEN: Reduce glucose in PN if blood glucose >10mmol/L (Weiman 2017, Clin Nutr, 36:623)

How often do you measure blood glucose?

Every 4 hours

Every 6 hours

Every 8 hoursOther frequency

Frequency of blood glucose monitoringDoes reducing frequency of blood glucose testing in stable non ICU patients reduce costs without increasing episodes of hyperglycaemia? Pre and post guideline development data collected

n=171 Pre (n=86)

Post (n=85)

P value

Total number of tests 25 23 0.011

Number of tests/patient 3.6 2.9 <0.001

Mean glucose (mg/dL) 126 129 0.005

Conclusion: new guideline reduced number of tests by 20% impacting cost and patient comfort without increasing blood glucose or glycaemic events

Ratliff et al (2018) Nut Clin Pract, in press. https://onlinelibrary.wiley.com/doi/pdf/10.1002/ncp.10020

Rebound hyperglycaemiaRebound hypoglycaemia with cyclical feeding?• Four studies comparing abrupt vs tapered in short term PN and no

difference1

Patients at risk• NBM• On Insulin• Octreotide

1. Stout & Cober (2010) Nutr Clin Pract;25:277

Do you measure blood triglycerides?

Yes

No

Once a dayOther frequency

Hypertriglyceridaemia Occurs if metabolic capacity to clear lipid exceeded

1. Llop et al (2003) Clin Nutr, 22:577

n = 260TG <3mmol/L

Days on PN ≥7 daysLipid 0.83±0.37g/kg

TG >3mmol/Ln=68 (26%)

62 (91%) ≥ 1 risk factorAKI

PancreatitisSteroids

Hyperglycaemia

Treatment

• Aim to avoid triglyceride >5mmol/dL, although evidence lacking1

• Take care where blood sampled• May need to discontinue PN for 4 hours• Should resolve on reducing lipid content• Avoid overfeeding from glucose

1. Braga et al (2009) Clin Nutr, 28:378. 2. Llop et al (2003) Clin Nutr, 22:577

Session outline

•Catheter related bloodstream infections•Glucose & lipid abnormalities•Parenteral nutrition associated liver disease•Micronutrient deficiencies

Abnormal LFTs

How common are abnormal LFTs in patients on PN?

Is it the PN?

Abnormal LFTs & short term PN• 58 patients receiving PN • 48 (83%) fistula, obstruction, ileus, failed EN

Baker & Nightingale (2004) Clin Nutr;23:864

• 60% LFTs worsened on PN• 30% LFTs resolved on PN

Abnormal LFTs before PN (34% patients)

• 46% sepsis• 24% underlying liver disease

Abnormal LFTs on PN (9% patients)

What are the causes of abnormal liver function tests?

What can we do to change this?

Causes

LFTsMedications

Sepsis

AKI/CKD

Pre-existing liver disease

Underlying disease

Gallstones

NBM

Gabe & Culkin (2010) Frontline Gastroenterology 1:98

Liver function testsFunction Causes of raised level (liver) Other causes

Bilirubin Breakdown of haem in RBC Cleared by hepatocytes Conjugated and secreted in bile

Hepatic: cirrhosis, viral hepatitis –would be associated with other abnormal LFTs

Prehepatic: ↑ bilirubin production (haemolytic anaemia, internal haemorrhage, Gilberts syndrome)Post hepatic: problem with excretion (obstruction of bile duct eg gallstones)

Alkaline phosphatase (ALP)

Enzyme in the cells lining the biliary ducts of the liver (but also bone & placental tissue)

Marked elevation in cholestasis (often with raised GGT more than ALT/AST), bile duct obstruction or infiltrating disease of the liver

Non liver causes more common if ALP raised in isolation. As ALP also present in bone, levels ↑ when increased bone turnover (adolescence, fracture) Pagets disease (elderly), metastasis and 3rd trimester of pregnancy

Alanine transaminase (ALT)

Aspartate aminotransferase (AST)

Enzymes normally inside hepatocytesALT more specific to the liver

AST also found in cardiac, RBC and skeletal muscle

Usually represent hepatocellular damage (viral hepatitis, paracetamol overdose) where marked ↑ seen

Raised AST may indicate issue with cardiac, RBC and skeletal muscle

Gamma-glutamyltransferase(GGT)

Related to bile ducts. May be ↑ with even minor, sub-clinical levels of liver dysfunction

Most common due to alcohol abuse (isolated ↑ or in combination with AST) Steatosis (fatty liver) or non-alcoholic steatohepatosis (NASH) caused by obesity & hyperlipidaemia

If NASH treat underlying causes such as raised cholesterol and obesity

Newsome et al (2018) Guidelines on the management of abnormal liver blood tests, Gut, 67:6

What can we do?

AssessMedications

Sepsis & collections

Liver screen

UltrasoundEnergy

requirements

Energy delivered

Lipid delivered

Evolution of lipid emulsionsGeneration Description Lipid types Brands

1st Conventional lipid LCT (soybean oil)LCT (soy/safflower oil) Intralipid

2nd Lipid emulsions with reduced PUFA

MCT/LCTStructured lipids (MCT/LCT)Olive oil

LipofundinStructolipidClinoleic

3rdLipid emulsions with reduced PUFA & specific ω6/ω3 FA ratio

Fish oilSoy/MCT/FOSoy/MCT/olive oil/fish oil

OmegavenLipidemSMOF

ASPEN: Clinical role for alternative intravenous fat emulsions (2012) Nut Clin Pract; 27:150. Raman et al (2017) Nutrients, 9:388

Lipid emulsions

Soya (LCT)High in n-6 → oxidative

stress, immune dysfunction/ inflammation

LCT/MCT Slower release into

bloodstream1

Reported benefitsNitrogen sparing2

Improved liver function3

LCT/Olive oil↓ n-6 ↑ n-9

Vitamin E: antioxidant

Reported benefits4,5

Liver function Oxidative stress

Immune function

Fish Oil↑n-3

Reported benefits immune

function6,7

Reduced length of hospital & ICU

stay8

1. Chambrier et al (2006) Nut Clin Pract, 21:342. 2. Lindgren et al (2001) Clin Nutr, 20:43. 3. Piper et al (2008) Eur J Anaesthesiol, 25:557. 4. Sala-Vila et al (2007) CurrOpin Clin Metab Care 10:165. 5. Wanten (2009) JPEN, 33:450. 6. Wang et al (2009) JPEN, 33:450. 7. Liang et al (2008) World J Gastroenterol, 14:p434. 8. Waitzberg & Torrinhas (2009) Nutr Clin Pract. 24:487

Choice of lipid

Soya (Intralipid)LCT/MCT (Lipofundin)LCT/Olive oil (ClinOleic) LCT/MCT/OO/FO (SMOF)

Lipid emulsions in PN

Which one should we use?Strength of evidence

Critical appraisal

Fish oils: A systematic reviewShort term PN

https://www.ncbi.nlm.nih.gov/pubmed/?term=Abbasoglu+2017+JPEN

Aim: To assess the quality of RCT investigating the use of parenteral fish oil (FO) lipid emulsionsQ: Does administering FO alone or as part of a multi-lipid emulsion improve outcomes

Assessed using Cochrane Collaboration criteria (grades bias as low, high or unknown risk)• Random sequence generation• Allocation blinding• Blinding of participants and personal• Blinding of outcome assessments• Incomplete outcome data• Selective reporting• Other bias

ResultsShort term PN

19 • Inflammatory & immune markers

13 • Infection or sepsis

29 • General clinical outcomes

3 • Clinical outcomes in sepsis

Conclusion: very little high quality evidence that fish oils have a beneficial effect

https://www.ncbi.nlm.nih.gov/pubmed/?term=Abbasoglu+2017+JPEN

Infusion ratesContinuous (over 24 hours)• Enables large volumes to be infused• Associated with continuous insulin secretion & lipogenesis

Cyclic (over 12-16 hours)• Permits mobilisation of free fatty acids from stores during non infusion period• Reduces risk of parenteral nutrition associated liver disease1

• Reduces thrombophlebitis in peripherally-fed patients2

• Enables rehabilitation/physiotherapy • Gradual wean from 24 hours

1. Hwang et al (2000) Hepatogastroenterology, 47:1347. 2. Kerin et al (1991) Clin Nutr, 10:315

Practical management of abnormal LFTsAcute IF (Type 1)• Look for other causes • Do not overfeed• Encourage oral• Daily lipid but what type is best? • Anti-inflammatory & anti-oxidative properties of fish oil is

attractive but limited evidence

Chronic IF (Type 2)• Look for other causes• Do not overfeed• Cyclical feeding• Limit lipid (<1g/kg/day)• Do not increase glucose calories to compensate• Decrease further/stop lipid• Use 2nd or 3rd generation but need more studies

Session outline

•Catheter related bloodstream infections•Glucose & lipid abnormalities•Parenteral nutrition associated liver disease•Micronutrient deficiencies

• Which tests analysed at your Trust?• What has to be sent away?• How long does it take to get results? • How do you interpret the results?

Micronutrients: what should you do?

Checking micronutrients

CRP <30

CRP <20CRP <10CRP <5

Duncan et al (2012) Am J Clin Nutr, 95:64. www.trace-elements.co.uk

A reliable clinical interpretation only if CRP <20 mg/L Zinc <10 mg/L Selenium and vitamins A and D <5 mg/L Vitamins B-6 and C

Vitamin D

• Common deficiency1

• Ergocalciferal 300,000IU IM stat dose• Second dose 3 months later, or by high dose oral therapy • Hospital oral liquid preparation 3,000 units/ml

• 15ml ONCE A WEEK • Does not contain gelatine or peanut oil. Suitable for

vegetarians, vegans, and those with nut allergies. Halal compliant

1. Fan et al (2017) Nutr Clin Pract, 32:258

Selenium Deficiency common1

High risk: CRRT, high U/O, diarrhoea/fistula output, multiple drains, steroids & statins2

Concentrations reduced during APRTreatment • IV 500ug for three days• Dilute 10mL of Selenase® in either 100mL or 250mL of 0.9%

sodium chloride solution or 5% glucose solution and infuse over 30 minutes

• Recheck concentration 4 weeks later• Try oral Selenase® 100-500ug/day• Double dose in PN or change to Nutryelt® or Addaven ®

1. Shenkin A. Selenium in intravenous nutrition. Gastroenterology 2009; 137: S61. 2. Jin et al (2017) Nutrients, 9:440

Zinc • Deficiency common1

• Bound to albumin• Concentrations reduced during APR• Major illness (CRP 100-200mg/L) causes a 40-60% reduction

and by 50% post-operatively2

• High GI losses

Treatment depends on concentration• Oral Solvazinc 45mg 1-3 times per day • Double dose in PN or change to Nutryelt® or Addaven®• Recheck concentration 4 weeks later

1. Jeejeebhoy K. (2009) Gastroenterology, 137: S7. 2. Jin et al (2017) Nutrients, 9:440

Conclusion

Monitoring vital to minimise complications

More robust RCTs required

Look for other causes of abnormal LFTs

MDT approach vital

Perfect area for supplementary prescribing