Systematic Review Scenario

The patient is a 46 year old male who is admitted with alcohol induced pancreatitis. His past medical history is significant for alcoholic cirrhosis and 40 pack years of smoking. The patient is admitted from the emergency department with a systolic blood pressure of 60 mm HG. He has no evidence of bleeding but is febrile. An abdominal CT scan is suspicious for infected pancreatic necrosis and he is taken to the operating room for debridement. The intraoperative cultures of the pancreatic fluid show gram negative rods. He was admitted to the ICU with a blood pressure of 70 mm hg. He had a profound capillary leak as evidenced by peripheral edema and his pulmonary artery catheter suggested hypovolemia. His albumin was 1.7 gm/dl. The patient’s surgeon suggested that you give the patient 5% albumin as a resuscitative fluid because the patient was hypoalbumenic. You stated that several recent systematic reviews suggest that the use of colloids may by associated with increased mortality in critically ill patients who are hypovolemic . You formulate the question, ‘In a critically ill patient with hypovolemia, does the use of colloids increase the risk of death compared to crystalloids?’

You search the Medline using the terms ‘albumin’ and ‘hypovolemia’ to identify the Cochrane Review that you remember hearing about. You find the appropriate citation in the BMJ.

• Is the evidence from this systematic review valid?
• Is this valid evidence from the systematic review important?
• Can you apply this valid and important evidence from this systematic review in caring for your patients?

Completed Systematic Reviews Worksheet for Critical Care Medicine

Citation

Roberts I. Cochrane injuries group albumin reviewers. BMJ 1998;317:235-240.

Are the results of this systematic review of therapy valid?

Is it a systematic review of randomised trials of the treatment you’re interested in?
Yes. it included trials with random allocation and quasi-random allocation .
Does it include a methods section that describes finding and including all the relevant trials?
Yes.
Does it include a methods section that describes assessing their individual validity?
Yes but did not use this data in the analysis and most studies had small sample size.
Were the results consistent from study to study?
Yes, insignificant test of heterogeneity.

Are the valid results of this systematic review important?

Translating odds ratios to NNTs. The numbers in the body of the table are the NNTs for the corresponding odds ratios at that particular patient’s expected event rate (PEER).
Odds Ratios
0.9 0.85 0.8 0.75 0.7 0.65 0.6 0.55 0.5
Patient’s Expected Event Rate (PEER) 0.05 209 1 139 104 83 69 59 52 46 41 2
0.10 110 73 54 43 36 31 27 24 21
0.20 61 40 30 24 20 17 14 13 11
0.30 46 30 22 18 14 12 10 9 8
0.40 40 26 19 15 12 10 9 8 7
0.503 38 25 18 14 11 9 8 7 6
0.70 44 28 20 16 13 10 9 7 6
0.90 101 4 64 46 34 27 22 18 15 125

Can you apply this valid, important evidence from a systematic review in caring for your patient?

Do these results apply to your patient?
No
How great would the potential benefit of therapy actually be for your individual patient?
Significant. For every 17 critically ill patients treated with albumin there will be one additional death.
Method I: In the table on page 1, find the intersection of the closest odds ratio from the overview and the CER that is closest to your patient’s expected event rate if they received the control treatment (PEER):
$$qquad text{NNT is 17 for death (95% CI 11 TO 33)}$$
Method II: To calculate the NNT for any OR and PEER:

$$text{NNT} = frac{1-[text{PEER}times(1- text{OR})]}{(1- text{PEER})times{PEER}times(1-text{OR})}$$

Are your patient’s values and preferences satisfied by the regimen and its consequences?
Do your patient and you have a clear assessment of their values and preferences?
Needs to be assessed in each patient.
Are they met by this regimen and its consequences?
Needs to be assessed in each patient.
Should you believe apparent qualitative differences in the efficacy of therapy in some subgroups of patients?

Only if you can say “yes” to all of the following:

• Do they really make biologic and clinical sense?
• Is the qualitative difference both clinically (beneficial for some but useless or harmful for others) and statistically significant?
• Was this difference hypothesised before the study began (rather than the product of dredging the data), and has it been confirmed in other, independent studies?
• Was this one of just a few subgroup analyses carried out in this study?

• In the subgroup analysis for hypoalbuminemic patients, the relative risk of death with albumin administration was 1.69 (95% CI 1.07 – 2.67).
• Most studies in this analysis were of poor quality and small sample size.

Hypovolemia: Albumin increases mortality in critically ill patients

Clinical Bottom Line

In critically ill patients, the use of albumin compared to crystalloid for volume resuscitation is associated with increased mortality.

Citation

Roberts I. Cochrane injuries group albumin reviewers. BMJ 1998;317:235-240.

Clinical Question

In critically ill patients, does the use of albumin compared to crystalloid for volume resuscitation increase mortality

Search Terms

Colloid and mortality in Cochrane.database of systematic reviews.

The Study

A systematic review of randomized clinical trials that evaluated whether the use of albumin compared with crystalloid for volume resuscitation is associated with mortality in critically ill patients.

The Evidence

Outcome CER EER RRR ARR [95% CI] NNT [95% CI]
Death in all patients 10% 16% 60% 6% [3% – 9%] 17 [11 – 33]

• The association between use of albumin and mortality was consistent across the subgroups analyzed:
• Hypovolemia RR of death with albumin: 1.46 (95% CI 0.97-2.22)
• Burns RR of death with albumin: 2.40 (95% CI 1.11 – 5.19)
• Hypoalbuminemia RR of death with albumin: 1.69 (95% CI 1.07-2.67)
• Many of the studies included in the analysis had weak methods. Most did not use blinded outcome assessment and most did not describe timing of the intervention of co-interventions. Nevertheless, none of the data suggest that the use of albumin is beneficial.

References

1. The relative risk reduction (RRR) here is 10%
2. The RRR here is 49%
3. For any OR, NNT is lowest when PEER = .50
4. The RRR here is 1%
5. The RRR here is 9%