TABLE 6.
Comparison of doses (unit doses, mean daily doses, and cumulative doses) and duration of treatment by gestational age for drugs commonly prescribed as a bolus (intermittent administration or single dose).
| Gestational age (weeks) | < 28 | 28-31 | 32-36 | ≥ 37 | Total | p* | Description of significant differences between GA groups† |
|---|---|---|---|---|---|---|---|
| Intermittent administration | |||||||
| Oral acetaminophen | n=1643 | n=2451 | n=4557 | n=8673 | n=17327 | ||
| Unit dose (mg/kg) | 15 (10-15) | 10 (10-15) | 10 (10-15) | 15 (15-15) | 15 (10-15) | < 001 | Unit dose for ≥ 37wks higher than other groups (P-values<.001). Unit dose of < 28 wks higher than 28-32 and 32-36 wks (P-values<.001). |
| Mean daily dose (mg/kg/d) | 40 (30-60) | 37 (30-60) | 40 (40-60) | 60 (60-60) | 60 (40-60) | < 001 | Daily dose for ≥ 37wks higher than others (P-values<0.001). 32-36 wks higher than < 28 and 28-31 wks, < 28 wks higher than 28-31 wks (P-values<.001). |
| Cumulative dose (mg/kg) | 359 (121-988) | 217 (90-632) | 191 (89-466) | 165 (91-301) | 181 (93-414) | < 001 | Differences between all groups: the lower the GA, the higher the cumulative dose (P-values<.001). |
| Duration of treatment (d) | 9 (3-24) | 6 (3-18) | 5 (2-11) | 3 (2-6) | 4 (2-9) | < 001 | Differences between all groups: the lower the GA, the higher the longer of treatment (P-values<.001). |
| IV acetaminophen | n=2069 | n=2436 | n=3221 | n=5286 | n=13012 | ||
| Unit dose (mg/kg) | 10 (10-15) | 10 (10-15) | 10 (10-20) | 7.5 (7.5-10) | 10 (10-15) | <.001 | Unit dose for ≥ 37wks lower than others (P-values<.001). |
| Mean daily dose (mg/kg/d) | 23 (20-35) | 20 (20-29) | 30 (30-40) | 30 (30-40) | 30 (25.5-40) | <.001 | Daily dose for ≥ 37wks higher than others, 32-36 wks higher than < 28 wks and 28-31 wks, < 28 wks higher than 28-31 wks (P-values<.001). |
| Cumulative dose (mg/kg) | 212 (90-409) | 122 (60-240) | 110.5 (58-209) | 80 (44-157) | 107 (54-223) | <.001 | Differences between all groups: the lower the GA, the higher the cumulative dose (P-values<.001, except between 28-31 wks and 32-36 wks P=.02). |
| Duration of treatment (d) | 7 (4-16) | 6 (3-10) | 4 (2-7) | 3 (2-5) | 4 (2-8) | <.001 | Differences between all groups: the lower the GA, the longer the duration of treatment (P-values<.001). |
| Oral morphine | n=619 | n=201 | n=344 | n=870 | n=2034 | ||
| Unit dose (µg/kg) | 100 (50-167) | 83 (50-150) | 83 (50-167) | 83 (50-167) | 88 (50-167) | .06 | |
| Mean daily dose (µg/kg/d) | 477 (277-729) | 417 (295-628) | 480 (340-778) | 480 (320-800) | 480 (312-800) | .002 | Daily dose for ≥ 37wks higher than < 28 wks (P=.02) and 28-31 wks (P=.01). |
| Cumulative dose (µg/kg) | 2417 (949-5763) | 2198 (975-4848) | 1820 (840-3906) | 1945 (863-4781) | 2066 (896-4842) | .049 | Cumulative dose for < 28 wks higher than 32-36 wks (P=.04). |
| Duration of treatment (d) | 7 (3-12.5) | 6 (3-12) | 4 (2-9) | 5 (2-10) | 5 (2-11) | <.001 | Duration of treatment for < 28 wks higher than 32-36 wks and ≥ 37wks (P-values<.001). Duration of treatment for 28-31 wks higher than 32-36 wks (P=.009) and ≥ 37 wks (P=.04). |
| IV morphine | n=74 | n=51 | n=62 | n=66 | n=253 | ||
| Unit dose (µg/kg) | 39 (10-50) | 50 (25-50) | 50 (20-50) | 50 (20-50) | 50 (20-50) | .04 | No difference between groups. |
| Mean daily dose (µg/kg/d) | 120 (40-196) | 150 (110-300) | 150 (127-300) | 150 (150-240) | 150 (90-250) | .002 | Mean daily dose for < 28 wks lower than others P=.04 vs 28-31 wks, P=.01 vs 32-36 wks and P=.007 vs ≥ 37 wks). |
| Cumulative dose (µg/kg) | 150 (51-312) | 169 (86-380) | 178 (69-390) | 150 (93-358) | 150 (63-360) | .46 | |
| Duration of treatment (d) | 1 (1-3) | 1 (1-2) | 1 (1-2) | 1 (1-2) | 1 (1-2) | .50 | |
| Single doses | |||||||
| Ketamine | n=846 | n=817 | n=753 | n=878 | n=3294 | ||
| Unit dose (mg/kg) | 1 (0.5-2) | 1 (0.5 -1) | 1 (0.5-2) | 1 (0.5-2) | 1 (0.5-2) | <.001 | Unit dose for ≥ 37wks higher than other groups (P-values<.01), 28-31 wks lower than < 28 wks (P=.01) and 32-36 wks (P<.001). |
| Propofol | 500 | 551 | 496 | 532 | n=2079 | ||
| Unit dose (mg/kg) | 1 (1-1) | 1 (1-1) | 1 (1-1) | 1 (1-1) | 1 (1-1) | <.001 | Unit dose for ≥ 37wks higher than others (P=.01 vs 32-36 wks and P-values<.001 vs others). Unit dose of 32-36 wks higher than 28-31 wks (P=.001). |
| Sufentanil | n=202 | n=84 | n=59 | n=56 | n=401 | ||
| Unit dose (µg/kg) | 0.2 (0.2-0.2) | 0.2 (0.2-0.2) | 0.2 (0.2-0.2) | 0.2 (0.2-0.5) | 0.2 (0.2-0.5) | <.001 | Unit dose for ≥ 37wks higher than <28 wks (P<0.001), 28-31 wks (P=0.03) and 32-36 wks (P=.007). |
| Atracurium | n=136 | n=44 | n=36 | n=54 | n=270 | ||
| Unit dose (mg/kg) | 0.3 (0.3-0.3) | 0.3 (0.25-0.3) | 0.3 (0.25-0.32) | 0.3 (0.25-0.3) | 0.3 (0.25-0.3) | .73 | |
GA: gestational age in weeks (wks), d: days, IV: intravenous. Doses and duration of treatment are described by their medians (interquartile range).
*P-value by the Kruskal-Wallis test. †Description of post-hoc analysis with Wilcoxon signed-rank test and Bonferroni correction.