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Corresponding author: Anne Holmberg Department of anesthesiology, Oslo University Hospital, P.O. Box 4956 Nydalen, 0424 Oslo, Norway. Ph: +47-481 27 279. Fax: +47 22 11 98 56. E-mail address: [email protected]
Microcirculation and haemodynamics after infraclavicular brachial plexus blocks using adrenaline as an adjuvant to lidocaine; a randomised, double-blind, crossover study in healthy volunteers A. Holmberg,1 A. V. T. Ho,2 D. Fernand,3 K. Toska,4,5 T. Wester ,6 Ø. Klaastad,7 T. Drægni8 and A. R. Sauter1,9 Institutional affiliations: 1 Consultant, Department of Anaesthesiology, Oslo University Hospital, Oslo, Norway 2 MD, Ph D student, Faculty of medicine, Section for physiology, University of Oslo, Oslo Norway 3 Student, Faculty of medicine, Section for physiology, University of Oslo, Oslo Norway 4 Professor, Faculty of medicine, Section for physiology, University of Oslo, Oslo Norway 5 Consultant, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway 6 Consultant, Department of Surgery, Section for plastic and recontructive surgery, Østfold Hospital Trust, Moss, Norway 7 Consultant, Department of Anaesthesiology, University Hospital of North Norway, Tromsø, Norway
8Research nurse, Department of Research and Development, Oslo University Hospital, Oslo, Norway
9 Consultant, Department of Anaesthesiology and Department of Research and Development, Division of Emergencies and Critical Care, Oslo University hospital, Oslo, Norway, Twitter: @ax_sauter Correspondence to: Dr A. Holmberg, [email protected] Short title: Circulatory changes after brachial plexus block Key words: brachial plexus block, microcirculation, adrenaline, heart rate, hemodynamics E-mail adresses for all authors: Anne Holmberg: [email protected] Ai Van Thuy Ho: [email protected] Dmitry Fernand: [email protected] Karin Toska: [email protected] Torjus Wester: [email protected] Øivind Klaastad: [email protected] Tomas Drægni: [email protected] Axel R. Sauter: [email protected] We are sorry, but most of the authors do not use twitter. We have added twitter handles only for the auhor who use the social networking service.
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Summary
We evaluated the effect of adrenaline when added to lidocaine in infraclavicular brachial plexus
blocks on human skin microcirculation (nutritive and subpapillary) and systemic cardiovascular
variables. Twelve healthy, non-smoking, male volunteers were included, each attending two study
sessions two weeks apart, with a crossover design. In both sessions, they received an ultrasound-
guided infraclavicular brachial plexus block in the non-dominant arm with 0.4 ml.kg-1 lidocaine 15
mg.ml-1 with or without adrenaline 5 µg.ml-1. Microcirculation was assessed by laser Doppler
fluxmetri (subpapillary blood flow), capillary video microscopy (nutritive blood flow), and continuous
temperature measurements. Heart rate and arterial pressure were recorded continuously and non-
invasively. Median (IQR [range]) subpapillary blood flow increased substantially 30 minutes after the
brachial plexus block, from 8.5 (4.4-13.5[2.9-28.2]) to 162.7(111.0-197.8[9.5-206.7]) arbitrary units
with adrenaline (p=0.017), and from 6.9(5.3-28.5[1.8-42.1] to 133.7(16.5-216.7[1.0-445.0] arbitrary
units without adrenaline (p=0.036). Nutritive blood flow (functional capillary density, capillaries.mm-
2, measured at the dorsal side of the hand) decreased in the blocked extremity when adrenaline was
used as adjuvant, from median (IQR [range]) 45(36-52[26-59]) to 38(29-41[26-42]) (p=0.028),
whereas no significant change occurred without adrenaline. Median (IQR [range]) finger skin
temperature (degrees Celsius) increased by median 44% (data pooled) with no significant differences
between the groups. No significant changes were found in the systemic cardiovascular variables with
or without adrenaline. We conclude that lidocain infraclavicular brachial plexus blocks cause an
increase in skin subpapillary blood flow. The addition of adrenaline gives more strong and long-
lasting blocks, but decrease the nutritive blood flow.
3
Introduction
Brachial plexus blocks are often used to provide analgesia and anaesthesia for upper limb surgery. A
block of the sympathetic fibers following the brachial plexus block will also increase peripheral blood
flow and skin temperature [1-4]. Brachial blocks are therefore used with the intention to improve
peripheral circulation after microvascular procedures, reconstruction surgery after traumatic
amputation, in treatment of vasospasm induced by Raynaud disease, and in treatment of peripheral
embolism [5,6].
The sympathetic blockade, any systemic uptake of local anaesthetics or adjuvants may induce
changes in blood pressure and cardiac output. Adrenaline is commonly added as an adjuvant to local
anaesthetics to prolong the duration of anaesthesia and reduce the peak plasma level of local
anaesthetics [7,8]. Systemic effects of adrenaline include increased heart rate, contractility and
arterial blood pressure. Locally, adrenaline causes vasoconstriction in the skin through an alfa-
adrenergic effect, whereas binding to beta-adrenergic receptors in arterioles in skeletal muscle
induce vasodilation [9].
Comparing brachial plexus blocks with and without adrenaline, McGregor et al. found a greater
increase in blood flow to the arm and a higher temperature rise when adding adrenaline to an
axillary brachial plexus block [10]. The authors suggested that these findings were caused by the
systemic effect of adrenaline inducing a rise in cardiac output. However, peripheral blood flow is
known to consist of two different components, which differ in their importance on perfusion of
tissue cells: the subpapillary blood flow which is controlled by synchronous opening or closing of
arteriovenous anastomosis for thermoregulation, and the nutritive blood flow in capillaries to cells in
skin and muscle[11]. A blockade of vasoconstrictive sympathetic nervous impulses to blood vessels,
for instance with adrenaline added to the block, is expected to increase both local nutritive blood
flow to skin and muscle, as well as increase blood flow through arteriovenous anastosmoses[12].
4
However, the effect of adrenaline adjuvant on these two different vascular entities have not been
studied in detail, to our knowledge, so far.
The aim of our study was to investigate the effect of adrenaline when added to lidocaine in
infraclavicular brachial plexus block on human skin microcirculation, both subpapillary blood flow
and nutritive blood flow, as well as the general systemic cardiovascular variables [13,14]. For our
primary aim, we tested the hypothesis that adrenaline added to lidocaine in brachial plexus block
cause alterations in both subpapillary blood flow and nutritive blood flow. Secondarily we tested if
the addition of adrenaline may cause changes in systemic cardiovascular variables. At last, we
wanted to characterize the time course of changes in blood flow to the blocked arm and control arm
as well as the characteristics of block with or without adrenaline adjuvant.
5
Methods
The protocol of this randomized, double blind, prospective, crossover study in healthy volunteers
was reviewed and approved by the Regional Committee for Medical Research Ethics in South-Eastern
Norway (2012/2189b) and the Norwegian Medicines Agency. The trial was registered in the EU
Clinical trials Register (EudraCT number 2012-005651-17) prior to enrolment of volunteers started. It
was conducted in adherence to guidelines for Good Clinical Practice. An external monitor from
Akershus University hospital monitored the study. This manuscript adheres to the applicable
CONSORT guidelines.
Twelve healthy, non-smoking male volunteers, age 18 – 60, American Society of Anesthesiologists
(ASA) physical status 1 or 2 with body mass index 18-35 kg.m-2 were recruited by poster
advertisements, and included after informed written consent. The subjects fasted at least 6 hours,
and were instructed not to consume coffee, black tea or garlic 12 hours prior to the experiments. No
medication was allowed during the last seven days before the experiments. Exclusion criteria were:
known nerve injury or nerve compression syndrome of the upper limb; diabetes mellitus; known
reduced immune response; any regular medication; and contraindications to lidocaine or adrenaline.
Each volunteer attended two study sessions two weeks apart, following an AB/BA crossover setup. In
both sessions, the participants received an ultrasound guided infraclavicular brachial plexus block in
the non-dominant arm. A volume of 0.4 ml.kg-1 lidocaine 15 mg.ml-1 was injected, either with or
without adrenaline 5 µg.ml-1. The sequence of blocks, i.e. if adrenaline was added in the first or the
second session, was randomized by computer-generated codes and packed in sealed envelopes by a
person not involved in the experiments. In each experiment, the local anaesthetic solution (with or
without adrenaline) was provided in two 20 ml syringes by an investigator not taking part in the
conduction of the experiment, thus the volunteers and all investigators present at the experimental
sessions were blinded to group allocation.
6
The volunteers were placed in the supine position in an operating theatre with controlled room
temperature of 21°C for 20 minutes. In order to keep the subjects relaxed, the investigators were as
quiet as possible during the experiments and soothing music was played in the room. An intravenous
line was established in the contralateral arm to the block. Standard monitoring including ECG, pulse
oximetry, and upper arm non-invasive blood pressure was applied.
Lateral sagittal infraclavicular block
An ultrasound-guided lateral sagittal infraclavicular brachial plexus block was performed in a
standardized way by one of the authors (ARS) as described in previous publications [15,16]. A Phillips
HD 11 XE ultrasound unit (Philips Medical Systems, Bothell, WA, USA) with a C8-5, 5 to 8 MHz, curved
linear transducer was used. A 22-gauge, 80mm Sono Plex Stim cannula (Pajunk GmbH, Geisingen,
Germany) was placed under ultrasound guidance, in-plane in a central position to the plexus, cranio-
posterior and close to the axillary artery. Start of block was defined as the time when the injecting
needle was withdrawn (‘needle out’).
The effect of the blocks was assessed after all measurements were completed, 60 min after local
anaesthetics injection. Sensory testing included the musculocutaneous, radial, median, ulnar, and
medial antebrachial cutaneous nerve. Blocks were assessed by temperature testing, using an ice bag
repeatedly touching the skin on predefined positions in the sensory area of the nerves. A sensory
block was considered successful when the volunteer had either no sensation for cold or touch
(anaesthesia) or no sensation for cold (analgesia). Motor testing included the musculocutaneous,
radial, median and ulnar nerve. A motor block was considered successful when the subjects had less
than 50% of normal muscle power as estimated by the examiner. To estimate block duration, the
volunteers were asked to report the first time after the block when they were able to hold and drink
from a cup with the blocked arm.
7
Laser Doppler measurements
Laser Doppler Fluxmetry (LDF) (MBF3D, Moor Instruments, Devon, UK) was used to measure
continuous skin blood flow from the left and right hypothenar, expressed in arbitrary units (AU). A
low-energy monochromatic laser beam is reflected from red blood cells 1 – 2 mm below the skin
surface [17,18]. This permits measurement of blood flow mainly in the subpapillary vessels, including
the arteriovenous anastomoses, where the blood flow is primarily serving a temperature-regulating
purpose[11]. The laser Doppler probes were fixed to the skin with double-sided tape. The noise-
limiting filter of the instrument was set at its highest level (21 kHz), and the emitted wavelength was
820 mm. The flux output signal was filtered with a time constant of 0.1 second and sent to the
recording computer. The sampling frequency was 2 Hz.
Capillary video microscopy
Capillary video microscopy with a few micrometres penetration depth was used to assess the
nutritive circulation of the skin. This permits assessments of both the functional density and the flow
velocity of visible capillaries. It was performed twice with a handheld digital microscope (GT700 UV,
Firefly, Belmont, MA, USA), first after 20 minutes of acclimatization and again 30 minutes after the
brachial plexus block, by one of the investigators (AH). Baby skin care oil (Sebamed®, Boppard,
Germany) was applied on the skin before examination. The microscope was then placed between the
first and second metacarp on the dorsal side of both hands. The hand of the side to be blocked was
examined first. Five video sequences were recorded for each examination, each video lasting 15
seconds. The recorded sequences were subsequently analysed using the software QuickTime Player
10.4 for MAC (Apple Inc., Cupertino, CA, USA) using a ME32C colour display unit (Samsung
electronics, Surrey, UK). Xscope software for MAC (the Iconfactory, Greeensboro, NC, USA) was used
to create a grid dividing the screen into 16 equal squares. Capillaries were counted in the four central
squares. When artefact occurred in any of the selected squares, four alternative adjacent squares
8
were randomly chosen. Average numbers from the capillary counts of two investigators (AH, ARS)
were used for analyses of functional capillary density (average number of counted papillary loops per
mm2).
A third investigator (TW) with broad experience in capillary flow assessment examined the flow
velocity. The flow was classified into five different categories: 0) No flow; 1) Sluggish flow; 2)
Continous low flow; 3) Continous high flow; 4) Brisk flow [19].
Temperature measurements
Thermocouples were attached to the digital pulp of finger 1, 2, 4, and 5 on both hands, excluding the
middle finger with the blood pressure cuff. The temperatures were continuously sampled at 1-
minute intervals with a multi-channel Hydra Series II data logger (Fluke, Everett, WA, USA) and
transferred for storage to a recording computer. Due to technical failure we had to replace the Hydra
Series II data logger and used a C28 K type thermometer (Comark, Norwich, UK), with temperature
measurements every 5 minutes on two volunteers on day two. A Hydra Series III (Fluke, Everett, WA,
USA) data logger was used for one volunteer on day two.
Non-invasive continuous hemodynamic monitoring
Heart rate (HR) was calculated over each R-R interval of a three lead electrocardiogram (ECG). Finger
arterial blood pressure was recorded continuously and non-invasively from the third finger of both
hands, using two Nexfin measurement devices (Nexfin®, BMEYE B.V., Amsterdam, the Netherlands).
Blood pressure measurements were performed on both sides to have comparable situations on the
blocked extremity and on the control arm. Only the recording from the dominant hand, which was
not used for plexus block, is reported. Both hands were placed on the arm boards of the operation
table in the height of the right atrium. The instantaneous blood pressure curve was transferred to a
9
recording computer where beat-to-beat mean arterial pressure (MAP) was calculated by integration
over each RR-interval.
The automatic self-calibration of the Nexfin disturbed minor parts of the recordings. After the
experiments, the MAP values measured during these calibration periods (3-5 heart beats) were
replaced by values obtained by interpolation from the MAP values on the beats immediately before
and after calibration. This was done with a custom-made computer program coded in MATLAB
(MathWorks inc, Natick, MD, USA).
Statistical methods and data analysis:
The main hypothesis was that adding adrenaline to a brachial plexus block cause alterations in both
components of skin blood flow. Based on pilot measurements (with a comparable setup as we used
in our study) we used the Doppler flow for statistical power analyses. We expected average Doppler
flow measurements around 40 arbitrary units (AU) and a SD of 20 AU. Based on previous studies and
our own pilot measurements, we expected an increase in blood flow of at least 50% [10]. A sample
size of 10 volunteers would have 80% power to detect a difference in means of 50% assuming
average laser Doppler flow rates of 40 AU (mean1) and 60 AU (mean2) with a common standard
deviation of 20 AU (with 0.5 covariance), using a 2-sided one-sample t-test with alpha 0.05. To
compensate for a lower efficacy of a non-parametric (Wilcoxon rank-sum) test we increased the
number by 15% to a sample size of 12 volunteers.
In order to calculate an average time course of the cardiovascular responses to the brachial block,
the median value from all subjects was calculated in each separate time bin of 0.1 second for the
cardiovascular variables. The mean temperature of the four fingers on each hand was calculated for
each time bin of 1 minute, and the median response from all subjects was calculated.
10
Data were entered into an Access CRF database and further analysed by IBM SPSS, version 25.0 (SPSS
Inc., Chicago, IL, USA). As a result of the small sample size, non-parametric methods were used and
data are presented as median, interquartile range and range. Wilcoxon rank-sum test for paired
samples are used for all data except for evaluating block success, when Pearson Chi Square test with
Yates correction is used. P-values smaller than 0.05 are considered statistically significant.
Considering the exploratory nature of the study, no adjustment for multiple testing/estimation was
performed for the primary or secondary outcomes.
11
Results:
Twelve male volunteers were included after given written informed consent. An incorrect group
allocation occurred in one participant who mistakenly received treatment without adrenaline twice.
The data set of this volunteer was therefore excluded. Furthermore, 3 more subjects were excluded
from the cardiovascular analyses, due to technical errors during the recordings. Because of functional
failure with the microscope, functional capillary density is missing for one of the subjects after
brachial plexus block with adrenaline.
The median (IQR [range]) age, weight, height, and BMI were 22(21-27[19-53]) years, 77(66-86[61-
95]) kg, 180(174-186[169-200]) cm, and 22.5(21.5-23.8[20.5-29.3]) kg.m-2, respectively. Median (IQR
[range]) injected volume of lidocaine in the blocks was 31(26-34[24-38]) ml, either with or without
adrenaline 5 µg.ml-1.
Block assessment
During the experiments, all volunteers reported a subjective feeling of effective blocks. At block
assessment one hour after initiation of the blocks, block success according to our strict predefined
criteria was significantly higher in the blocks with adrenaline. Complete sensory blockade of all distal
nerves (musculocutaneous, radial, median, ulnar, and medial antebrachial cutaneous nerve)
combined with complete motor blockade of all distal nerves (musculocutaneous, radial, median and
ulnar nerve) was seen in 10 (91%) of the blocks with adrenaline and 2(18%) of the blocks without
adrenaline, p=0.003. Median (IQR [range]) block duration (tested by obtained motor control) was
203(125-230[113-285]) min in the blocks with adrenaline and only 67(62-72[30-93]) min in the blocks
without adrenaline (p=0.003).
Laser Doppler measurements
12
A substantial increase in blood flow was observed in all subjects in the blocked arm, both in blocks
with adrenaline and blocks without adrenaline (figure 1, table 1, table 2). There was no statistically
significant difference in blood flow between block with and without adrenaline in the blocked arm
(p=0.889) (figure 1).
Capillary video microscopy
Functional capillary density decreased 30 min after brachial plexus block with adrenaline compared
with pre-block measurements in the blocked arm (figure 2, table 1, table 2). After the blocks without
adrenaline, no significant decrease was found (table 1, table 2). However, functional capillary
density was always significantly lower in the blocked arm compared to the control arm 30 min after
block (p=0.005 with adrenaline, p=0.033 without adrenaline). We did not find a statistically
significant difference in functional capillary density when comparing brachial plexus block with and
without adrenaline (p=0.074).
No significant changes were found for the capillary flow patterns and flow velocity.
Temperature measurements
Thirty min after brachial plexus block, we found increased temperature in the blocked arms
compared to the pre-block measurements in both the blocks with and without adrenaline (table 1).
The temperature changes were also significantly higher in the blocked arm compared to the control
arm in both types of block (table 2). Adrenaline delayed the onset of the temperature change in the
fingers. Time to half temperature rise in minutes (median (IQR [range])) was 11.0(9.4-15.5[6.6-26.0])
minutes with adrenaline and 7.6(3.7-11.2[0.0-14.4]) minutes without adrenaline, p= 0.013. Thirty
minutes after the block, no statistically significant temperature differences were found when
comparing brachial plexus block with and without adrenaline (p=0.074).
13
Non-invasive continuous hemodynamic monitoring
After brachial block, no substantial changes in MAP were seen, neither with nor without adrenaline
(figure 1, table 1). We did not find a statistically significant difference in HR and MAP when
comparing brachial plexus block with and without adrenaline (p=0.674 and p=0.575).
14
Discussion:
Our study shows an increase in hypothenar subpapillary skin blood flow after infraclavicular brachial
block in the anaesthetized extremity. Skin temperature increased correspondingly. In contrast,
nutritive blood flow to the skin on the dorsal side of the hand decreased when adrenaline was used
as an adjuvant. Compared with the control arm, nutritive blood flow to the skin was lower after
blocks with and without adrenaline. The use of adrenaline had no significant effect on cardiovascular
variables, but resulted in stronger nerve blocks.
Peripheral nerve blocks decrease the intensity of sympathetic nervous signals transmitted by
noradrenaline to blood vessels in the arm, both in muscles and skin. A block of the sympathetic nerve
fibres innervating the arteriovenous anastomosis in the glabrous (non-hairy) skin increases blood
flow in the palms and fingers [4]. In our study a substantial increase in blood flow in the blocked arm
was observed after infraclavicular brachial plexus blocks. However, the sympathetic block did not
increase blood flow to the nutritive arterioles in the non-glabrous skin on the dorsal side of the hand
were arteriovenous anastomosis are not present. On the contrary, we found lower functional
capillary density after infraclavicular blocks compared with the control arm, indicating a decreased
skin microcirculation in this area. This observation could be explained by a steal effect caused by the
increase in blood flow to the arteriovenous anastomosis in the palms and fingers [20]. Circulating
adrenaline may also cause direct vasoconstriction in nutritive blood flow to the skin. The
vasoconstrictive effect might increase when there is a steal effect in the arteriovenous anastomosis
due to the sympathetic blockade.
When we evaluated the blocks after about 60 minutes, we found significantly better blocks and
higher block success in the adrenaline group compared with the non-adrenaline group. We evaluated
all five distal nerves, and considered all partly failed blocks as failed blocks. Another definition of
block success, as suggested by Asghar et al, use increase in skin temperature as a valid and reliable
15
measure for predicting successful infraclavicular blocks [21]. According to this definition, all blocks
would be considered successful during the first 30 min. Several participants reported a subjective
feeling of an early block resolution after the no-adrenaline blocks before the scheduled block
evaluation after 60 minutes, which indicates that the blocks were about to wear out at block
evaluation.
Similar observations as ours on block quality were reported by Dogru et al when comparing the
effect of high doses of adrenaline with no adrenaline for axillary plexus blocks with lidocaine [22].
Adrenaline prolonged the duration of the blocks due to vasoconstriction at the injection site and
slower diffusion of local anaesthetics into the nerve fibres. The longer duration and better quality of
the adrenaline blocks in our study can explain the greater changes in subpapillary and nutritive blood
flow. Better block quality after addition of adrenaline might also cause a stronger steal effect to the
nutritive skin perfusion compared with the blocks without adrenaline.
Using continuous non-invasive monitoring we did not observe an effect of adrenaline on systemic
cardiovascular variables like heart rate or blood pressure. We can therefore presume that adrenaline
had little or no systemic effect that can explain the results of our study. The systemic effect of
adrenaline might depend on the volume and the injection site. A previous study by Dogru et al.
showed that low doses of adrenaline offered more stable hemodynamics (blood pressure and heart
rate), but similar block quality compared with high doses [22]. A recent study on paracervical blocks
showed a highly significant increase in blood pressure, heart rate and cardiac output when
adrenaline was used as an adjuvant to bupivacaine [23].
Laser Doppler was used in several studies to investigate changes in skin perfusion after brachial
plexus blocks, all of them reporting alterations in circulations. Arterial vasodilatation, increase in
blood flow velocity, and increase in blood flow through the ipsilateral brachial artery have been
16
shown after axillary brachial plexus blocks [24]. Landsverk et al observed alterations in the oscillatory
components of the flowmetry signal in the blocked arm and the contra-lateral arm. However, blood
flow was not significantly increased in this study [2]. Interestingly, the group measured skin perfusion
on the volar side of the hand where arteriovenous anastomosis are not present. Lethipalo and
colleagues observed increased skin perfusion in the index finger after interscalene brachial plexus
block [25].
Our findings may have important implications for the clinical setting: Brachial plexus blocks increase
subpapillary blood flow in glabrous skin. On the other hand, the nutritive blood flow to the non-
glabrous skin decreases after the blockade with adrenaline adjuvant, which enhance the block
strength and duration. From these findings it may be speculated that adrenaline adjuvant is to be
recommended when a strong block for surgery or pain relief is required, whereas a block without
adrenaline may be recommended if the purpose of the block is to increase the microcirculation and
oxygenation of peripheral cells. Both aspects should be considered when brachial plexus blocks are
performed to enhance vascular microcirculation.
Our study has several limitations. All our participants were healthy and non-smoking. In a clinically
setting, this is not always the case. We did not include women because female reproductive
hormones may influence on the non-noradrenergic mechanisms of vasoconstriction [26]. Our
participants were predominantly young, thus the results may not apply in older patients because of
age related alterations in skin blood flow. Further, an acclimatisation period of 20 minutes might
have been to short and may have resulted in changes in the measurements in the control arm during
the course of our registrations. Our results only applies to infraclavicular blocks with lidocain 15
mg.ml-1 using adrenaline 5 µg.ml-1 as an adjuvant with an injection volume of 0.4 ml.kg-1. Because of
a small sample size in our study, we might have type 2 errors in our statistical calculations.
17
In conclusion, subpapillary skin blood flow increase after infraclavicular brachial plexus blocks,
whereas nutritive blood flow to the non-glabrous skin decreases. Adrenaline as an additive did not
have a significant effect on cardiovascular variables, but resulted in stronger nerve blocks and
possibly a more pronounced decrease in nutritive blood flow.
Competing interests:
Oslo University Hospital founded the complete work. In addition AH were 50% employed by a
scholarship from the South-Eastern Norway Regional Health Authority.
Acknowledgements:
Johan Raeder has kindly read through the paper and given constructive input to the manuscript
preparation.
18
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20
Table 1: Comparison of measurements before and 30 minutes after infraclavicular plexus block.
Blood flow (Laser Doppler), functional capillary density (FDC), and skin temperature was registered in
the blocked arm and the control arm. Heart rate and mean arterial pressure was measured
simultaneously. Lidocaine with and without adrenaline as an additive was used for the blocks. Values
are median (IQR [range]).
Adrenaline Side N Before block 30 min after block P-value
Blood flow
(AU)
Yes Block 8 8.5(4.4-13.5[2.9-28.2]) 162.7(111.0-197.8[9.5-206.7]) 0.017
Control 8 -0.8(-0.9-4.1[-0.9-5.4]) -0.8(-0.9-13.8[-0.9-18.2]) 0.036
No Block 8 6.9(5.3-28.5[1.8-42.1] 133.7(16.5-216.7[1.0-445.0] 0.036
Control 8 4.9 (-0.8-11.4 [-0.9-16.7]) 9.8(-0.7-21.9[-0.9-37.5]) 0.069
FDC
(Capillaries.mm-
2)
Yes Block 10 45(36-52[26-59]) 38(29-41[26-42]) 0.028
Control 10 40(34-53[31-65]) 48(42-58[40-70]) 0.005
No Block 11 39(35-49[29-51]) 40(33-44[30-56]) 0.594
Control 11 45(38-50[30-53]) 47(40-51[35-71]) 0.477
Temperature
(oC)
Yes Block 11 22.1(21.5-22.9[20.5-25.4]) 34.1(33.6-34.6[25.9-35.1]) 0.003
Control 11 22.0(21.7-26.3[20.4-28.9]) 21.5(21.0-22.1[20.1-23.4]) 0.006
No Block 11 22.4(21.5-25.7[20.8-29.6]) 33.9(31.4-34.5[20.8-34.8]) 0.004
Control 11 22.5(21.9-27.3[20.6-30.6]) 21.7(20.9-22.6[20.7-27.3]) 0.004
HR
(beats.min-2)
Yes 8 56.2(48.4-64.7[43.5-77.1]) 62.6(55.6-70.9[51.5-72.6]) 0.263
No 8 52.9(49.9-59.7[46.8-79.0]) 63.5(54.1-68.7[50.7-70.0]) 0.208
MAP
(mmHg)
Yes 8 95.8(91.8-111.8[91.3-122.0]) 101.6(88.0-114.6[70.3-125.2] 0.779
No 8 90.1(76.7-96.6[71.4-102.7]) 90.7(89.8-101.0[72.4-124.2]) 0.161
21
Table 2: Comparison of changes in blood flow (Laser Doppler), functional capillary density (FDC), and
skin temperature before block to 30 minutes after block in the blocked arm compared with the
unblocked (control) arm. Lidocaine with and without adrenaline as additive was used for the blocks.
Values are median (IQR [range]).
N Adrenaline Blocked arm Control arm P-value
∆ Blood flow
(AU)
8 Yes 142.0(107.4-189.2[-1.2-200.0]) 0.0(0.0-9.8[-0.0-13.5]) 0.017
8 No 120.5(-0.3-211.1[-0.9-413.9]) 1.9(0.0-11.3[-1.8-29.6]) 0.050
∆ FCD
(Capillaries.mm-2)
10 Yes -8.6(-15.2-1.4[-21.3-3.9]) 5.7(3.5-14.8[0.4-16.7]) 0.007
11 No -4.5(-8.1-6.7[-15.7-14.8]) 1.6(-4.1-12.5[-8.8-28.5]) 0.182
∆ Temperature
(oC)
11 Yes 11.8 (9.3-12.5 [4.4-14.2]) -0.7(-4.1-(-0.3) [-5.9-0.2]) 0.003
11 No 10.3(4.9-12.0 [-0.7-12.8]) -1.2(-3.4-(-0.2) [-5.2-0.1]) 0.004
22
Figure legends:
Figure 1:
A: Changes in subpapillary blood flow: Skin blood flow measured by laser Doppler in the blocked arm
and the non-blocked arm (control) after brachial block with and without adrenaline. B: Average
temperature in the four fingers in the blocked arm and non-blocked arm (control) after blocks with
and without adrenaline. C: Average beat-to-beat recordings of MAP. D: Average beat-to-beat
recordings of HR.
Figure 2:
Changes in nutritive blood flow: Picture A shows functional capillary density between the first and
second metacarp on the dorsal side of the hand before infraclavicular block. Figure B shows
functional capillary density in the same place in the same patient 30 minutes after infraclavicular
block with adrenaline.