Introduction
Materials and methods
Study design
Ethical approval
Patients
Body temperature measurements
Statistical analyses
Results
Patient characteristics
All patients, N =15,818
|
No paracetamol, n =5,772
|
Paracetamol, n =10,046
|
P
-value
| |
---|---|---|---|---|
Age, yr | 64 (51 to 73) | 62 (49 to 73) | 64 (52 to 73) | <0.001 |
Male sex | 64% (1,019) | 63% (3,631) | 65% (6,568) | 0.002 |
APACHE II score | 16.9 (7.18) | 17.7 (8.4) | 16.5 (6.3) | <0.001 |
SAPS II score | 29.5 (22.4) | 28.3 (26.2) | 30.2 (19.8) | <0.001 |
Hospital A | 20.3% (3,206) | 14% (786) | 24% (2,419) | <0.001 |
Hospital B | 10.9% (1,718) | 11% (631) | 11% (1,087) | 0.83 |
Hospital C | 10.2% (1,607) | 12% (707) | 9% (900) | <0.001 |
Hospital D | 58.7% (9,288) | 63% (3,648) | 56% (5,640) | <0.001 |
Mechanical ventilationb
| 73% (11,513) | 70% (4,032) | 74% (7,481) | <0.001 |
Acute renal failurec
| 6% (944) | 8% (477) | 5% (457) | <0.001 |
Surgical admissionsd
| 63% (9,994) | 51% (2,949) | 70% (7,045) | <0.001 |
Elective surgery | 49% (7,707) | 37% (2,154) | 55% (5,553) | <0.001 |
Infection as admission diagnosise
| 9% (1,419) | 9% (518) | 9% (901) | 0.99 |
Number of temperature measurements | 15 (9 to 36) | 11 (5 to 20) | 18 (11 to 49) | <0.001 |
Mean temperature, °C | 36.7 (0.7) | 36.6 (0.8) | 36.8 (0.6) | <0.001 |
Highest temperature, °C | 37.6 (1.0) | 37.4 (0.9) | 37.8 (1.0) | <0.001 |
Lowest temperature, °C | 35.4 (2.2) | 35.6 (1.9) | 35.4 (2.4) | <0.001 |
SD of temperature, °C | 0.62 (0.46) | 0.59 (0.50) | 0.64 (0.43) | <0.001 |
Temperature >38°Cf
| 28% (4,397) | 18% (984) | 34% (3,413) | <0.001 |
Temperature >38.3°Cf
| 20.3% (3,212) | 11% (647) | 26% (2,565) | <0.001 |
Temperature >38.5°Cf
| 15.5% (2,456) | 7% (429) | 20% (2,027) | <0.001 |
Temperature >39°Cf
| 7.9% (1,247) | 3% (174) | 11% (1,073) | <0.001 |
Temperature <35°Cf
| 37.6% (5,949) | 33% (1,927) | 40% (4,022) | <0.001 |
Total dose, g | 1 (0 to 4) | 0 (0 to 0) | 3 (2 to 7) | <0.001 |
Mean daily dose,g g | 1 (0 to 2) | 0 (0 to 0) | 1.9 (1.0 to 2.6) | <0.001 |
Outcomes
Survivors, N =13,654
|
Dead, N =2,164
|
P
-value
| |
---|---|---|---|
Age, yr | 63 (50–73) | 67 (55–76) | <0.001 |
Male sex | 65% (8827) | 63% (1372) | 0.26 |
APACHE II score | 15.46 (5.78) | 26.15 (8.13) | <0.001 |
SAPS II score | 26.9 (20.6) | 45.5 (26.1)) | <0.001 |
Hospital A | 21% (2870) | 15% (335) | <0.001 |
Hospital B | 11% (1474) | 11% (244) | 0.5 |
Hospital C | 10%(1300) | 14% (307) | <0.001 |
Hospital D | 59%(8010) | 59% (1278) | 0.73 |
Mechanical ventilationb
| 71% (9694) | 84% (1819) | <0.001 |
Acute renal failurec
| 71% (9694) | 84% (1819) | <0.001 |
Surgical admissionsd
| 4% (572) | 17% (362) | <0.001 |
Elective surgery | 69% (9398) | 28% (596) | <0.001 |
Infection as admission diagnosise
| 55% (7507) | 9% (200) | <0.001 |
Number of temperature measurements | 8% (1027) | 18% (392) | <0.001 |
Mean temperature, °C | 36.7 (0.6) | 36.6 (1.0) | <0.001 |
Highest temperature, °C | 37.6 (0.9) | 37.9 (1.4) | <0.001 |
Lowest temperature, °C | 35.5 (2.1) | 34.9 (2.6) | <0.001 |
SD of temperature, °C | 0.60 (0.45) | 0.78 (0.49) | <0.001 |
Temperature >38°Cf
| 26% (3469) | 45% (928) | <0.001 |
Temperature >38.3°Cf
| 18% (2441) | 36% (771) | <0.001 |
Temperature >38.5°Cf
| 13% (1812) | 30% (644) | <0.001 |
Temperature >39°Cf
| 6% (859) | 18% (388) | <0.001 |
Temperature <35°Cf
| 35% (4823) | 52% (1126) | <0.001 |
Number of patients given paracetamol | 66% (9050) | 46% (996) | <0.001 |
Total dose, g | 0 (0–0) | 3 (2–7) | <0.001 |
Mean daily dose,g g | 0 (0–0) | 1.9 (1.0-2.6) | <0.001 |
N
|
Adjusted OR (95% CI)
|
P
-value
|
Adjusted HR (95% CI)
|
P
-value
| |
---|---|---|---|---|---|
Allb
| 15,818 | 0.60 (0.53 to 0.68) | <0.001 | 0.51 (0.46 to 0.56) | <0.0001 |
Surgeryc
| |||||
Yes | 9,994 | 0.72 (0.58 to 0.91) | 0.006 | 0.51 (0.42 to 0.61) | <0.0001 |
No | 5,824 | 0.56 (0.48 to 0.66) | <0.001 | 0.51 (0.45 to 0.57) | <0.0001 |
Feverd
| |||||
Yes | 4,397 | 0.76 (0.61 to 0.93) | 0.009 | 0.57 (0.49 to 0.66) | <0.0001 |
No | 11,421 | 0.54 (0.46 to 0.64) | <0.001 | 0.49 (0.43 to 0.56) | <0.0001 |
Medical, fever and infectione
| 681 | 0.67 (0.42 to 1.05) | 0.08 | 0.47 (0.33 to 0.65) | <0.0001 |
Subgroup and sensitivity analysis
N
|
Adjusted HR (95% CI)
|
P
-value
| |
---|---|---|---|
Allb
| 15,818 | 0.68 (0.61 to 0.75) | <0.001 |
Surgeryc
| |||
Yes | 9,994 | 0.64 (0.53 to 0.77) | <0.001 |
No | 5,824 | 0.72 (0.64 to 0.81) | <0.001 |
Feverd
| |||
Yes | 4,397 | 0.84 (0.72 to 0.98) | 0.02 |
No | 11,421 | 0.58 (0.50 to 0.66) | <0.001 |
Medical, fever and infectione
| 681 | 0.70 (0.49 to 0.99) | 0.04 |
Discussion
Key findings
Relationship with previous studies
Study implications
Strengths and limitations
Conclusions
Key messages
-
Among critically ill patients, little is known about the association between paracetamol administration and patient outcomes.
-
We conducted a large multicenter study and found an independent association between paracetamol administration and greater survival to hospital discharge.
-
This association applied to surgical and medical patients and to febrile and non-febrile patients.
-
This association remained present after Cox proportional hazards analysis, propensity score adjustment, treatment of paracetamol administration as a time-varying variable and sensitivity analysis.